Software-defined implantable ultrasonic device for use in the internet of medical things

ABSTRACT

Implantable and wearable devices and system for transmitting signals ultrasonically through biological tissue are implemented based on an Internet of Medical Things (IoMT) platform software and hardware architecture. The devices are size-, energy-, and resource-constrained and implement ultrasonic communication protocols and communicate with each other through ultrasound.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. § 119(e) of U.S.Provisional Application No. 62/376,027, filed on Aug. 17, 2016, entitled“Software-Defined Implantable Ultrasonic Device for Use in the Internetof Medical Things,” the disclosure of which is hereby incorporated byreference.

This application claims priority under 35 U.S.C. § 120 of U.S. patentapplication Ser. No. 15/546,423, filed on Jul. 26, 2017, entitled“Internet-Linked Ultrasonic Network for Medical Devices,” which is anational phase entry under 35 U.S.C. § 371 of International ApplicationNo. PCT/US2016/014860, filed on Jan. 26, 2016, which claims priorityunder 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62/107,737,filed on Jan. 26, 2015, the disclosures of which are hereby incorporatedby reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under Grant NumberCNS-1253309 awarded by the National Science Foundation. The governmenthas certain rights in the invention.

BACKGROUND

Wirelessly networked systems of implantable medical devices endowed withsensors and actuators may be the basis of many innovative therapies.Existing as well as futuristic applications of wireless technology tomedical implantable and wearable devices are growing into a new marketthat several analysts are starting to refer to as “The Internet ofMedical Things” (IoMT). Unfortunately, the dielectric nature of thehuman body poses a key obstacle to enabling this vision of networkedimplantable devices. Biological tissues are composed primarily (65%) ofwater, a medium through which radio-frequency (RF) electromagneticwaves, which are the physical basis of most commercial wirelesstechnologies such as WiFi or Bluetooth, do not easily propagate. Thehuman body absorbs, distorts, and delays RF signals. Since RF waves areabsorbed by tissues, higher transmission power is needed to establishreliable communication links. This reduces the battery lifetime (or,equivalently, increases the battery size) of the implantable device, ina domain where low power, miniaturization, and battery duration aremajor concerns. A surgical procedure is, in most cases, needed toreplace the batteries of implants. To put this in context,state-of-the-art pacemakers require power in the order of μW for pacing,while a commercial RF transceiver for an implant operates with power inthe order of tens of mW, making continuous telemetry operationprohibitive. As a consequence, in state-of-the-art pacemakers, thebattery alone often occupies two thirds of the entire volume of theimplant.

SUMMARY OF THE INVENTION

A hardware and software architecture of an Internet of Medical Things(IoMT) platform with ultrasonic connectivity for communications throughbody tissues is provided. The IoMT platform incorporates a modular andreconfigurable hardware and software architecture that can be flexiblyadapted to different application and system requirements to enabletelemetry, remote control of medical implants, as well andimplant-to-implant communications for closed-feedback loop applications.

Additionally, embodiments of size-, energy-, and resource-constraineddevices are implemented based on the IoMT platform software and hardwarearchitecture, i.e., an implantable IoMT-mote and a wearable IoMT-patch,that implement ultrasonic communication protocols and communicate witheach other through ultrasounds. The IoMT-mote is a miniaturizedsoftware-defined implantable device with ultrasonic communication andnetworking capabilities. Embodiments of these devices are based onlow-power miniaturized components, providing miniaturized wirelessultrasonic implantable devices. In some embodiments, their performancecompares favorably with commercial RF-based wireless technologies, e.g.,Bluetooth Low Energy (BLE).

A telemetry system is provided that is based on the two devices forreal-time remote monitoring of biological parameters. The system cancomprise multiple IoMT-motes with sensing capabilities deployed inside ahuman body that communicate through ultrasounds with an IoMT-patchattached to the body. The IoMT-patch can offer RF wireless connectivityto route the sensed information to a smartphone or to the cloud.

Other aspects of the method, device, and system include the following:

1. An ultrasound communication device for transmitting signalsultrasonically within a network of implanted and/or worn medicaldevices, comprising:

a communication unit comprising an ultrasonic transceiver to transmitand receive ultrasonic signals through biological tissue to and fromother devices in the network of devices; and

a processing unit in communication with the communication unit toreceive signals from and transmit signals to the communication unit, theprocessing unit including a processor and memory, the processoroperative to reconfigure in real time one or more upper layer protocolsin a protocol stack and a reconfigurable logic device operative at aphysical layer in the protocol stack.

2. The device of embodiment 1, wherein the processor is operative toreconfigure one or more of an application layer, a link layer, a mediaaccess control layer, and a network transport layer.

3. The device of any of embodiments 1-2, wherein the reconfigurablelogic device is operative to control transmitter and receiver chains totransmit and receive ultrasonic transmissions.

4. The device of any of embodiments 1-3, wherein the reconfigurablelogic device includes a register module operative to store and routeconfiguration parameters determined by the processor, the configurationparameters including one or more of a spreading code, a spreading codelength, a time-hopping frame length, a time-hopping sequence, a packetpayload size, or a length of a preamble.5. The device of embodiment 4, wherein the processor delivers to theregister module the configuration parameters via a serial peripheralinterface.6. The device of any of embodiments 1-5, wherein the reconfigurablelogic device includes a configurable serial peripheral interface (SPI)module.7. The device of embodiment 6, wherein the SPI module is operative toconfigure communication settings, including one or more of data rate,clock polarity and clock phase.8. The device of any of embodiments 6-7, wherein the SPI module isoperative to enable communication with the processor or a peripheraldevice.9. The device of any of embodiments 6-8, wherein the SPI module includesa master module in communication with the processor and a slave module.10. The device of any of embodiments 6-9, wherein the SPI module isoperative to trigger sampling operations on an analog to digitalconverter and to read back sampled digital waveforms.11. The device of any of embodiments 1-10, wherein the reconfigurablelogic device includes a field-programmable gate array, amasked-programmed gate array, an application specific integratedcircuit, a small-scale integrated circuit, a programmable logic array,or a programmable logic device.12. The device of any of embodiments 1-11, further comprising a sensingor actuating unit, and wherein the controller is operative in real timeto trigger a reading from the sensing or actuating unit and to processthe reading.13. The device of embodiment 12, wherein the controller is furtheroperative to transmit data processed from the reading to the logicdevice for transmission as an ultrasonic signal.14. The device of any of embodiments 1-13, wherein the processing unitfurther includes an energy management module operative to adjust atruntime a core clock frequency according to processing power required,select at runtime a low-power mode, provide an automatic wake-up, orpower up and shut down components.15. The device of any of embodiments 1-14, wherein the communicationunit further includes a receiver chain including an analog to digitalconverter operative to convert incoming ultrasonic analog signals todigital signals, and a transmitter chain including a digital to analogconverter operative to convert outgoing digital signals to analogsignals for ultrasonic transmission.16. The device of any of embodiments 1-15, further comprising a sensorinterface to enable connection between the processing unit and a sensordevice or an actuating device.17. The device of any of embodiments 1-16 in communication with asensing device selected from the group consisting of a motion sensor, agyroscope, an accelerometer, a cardiac rhythm monitor, a heart ratemonitor, a pulse monitor, a blood pressure monitor, a glucose sensor, adrug pump monitor, a sleep sensor, a REM sleep duration sensor, a stillcamera, a video camera, a sensor for one or more biomolecules, a sensorfor one or more pharmaceutical agents or pharmaceutical formulationingredients, a sensor for a dissolved gas or ion, a sensor for pH, asensor for ionic strength, and a sensor for osmolality.18. The device of any of embodiments 1-17 in communication with anactuating device selected from the group consisting of a drug pump, aheart stimulator, a heart pacemaker, a bone growth stimulator, a deepbrain stimulator, a neurostimulator, and a neuromuscular electricalstimulator.19. The device of any of embodiments 1-18, wherein the device isimplantable within a body or wearable on a skin surface of a body.20. The device of any of embodiments 1-19, wherein the communicationunit further includes a radio frequency (RF) interface operative toreceive and transmit in-air RF transmissions, and wherein the device iswearable on a skin surface of a body.21. The device of embodiment 20, wherein the device is in communicationvia said RF transmissions with a further device coupled to acommunications network.22. The device of any of embodiments 20-21, further comprising awireless controller operative to connect to a Bluetooth Low Energy (BLE)access point device and/or to a 6LoWPAN device.23. The device of embodiment 22, wherein the wireless controllerincludes a Message Queue Telemetry Transport (MQTT) client module thatis operative to read data from the implantable device through theultrasonic interface, and publish sensor readings to an MQTT broker.24. The device of any of embodiments 22-23, wherein the wirelesscontroller includes a Message Queue Telemetry Transport (MQTT) clientmodule operative to open a connection with the MQTT broker through anIPv6 address, to authenticate an application, and/or publish newcontent.25. The device of any of embodiments 1-24, wherein the processor isoperative at a current of less than 7 mA during a run mode.26. The device of any of embodiments 1-25, wherein the processor isoperative at a current of less than 2 mA during a transmit state.27. The device of any of embodiments 1-26, wherein the processor isoperative at a current of less than 0.22 mA during a stop mode.28. The device of any of embodiments 1-27, wherein the processor isoperative at a current of less than 0.001 mA during a very low leakagemode.29. The device of any of embodiments 1-28, wherein the processor isoperative at a power level of less than 22 mW during a run mode.30. The device of any of embodiments 1-29, wherein the processor isoperative at a power level of less than 7 mW during a transmit state.31. The device of any of embodiments 1-30, wherein the processor isoperative at a power level of less than 0.6 mW during a stop mode.32. The device of any of embodiments 1-31, wherein the processor isoperative at a power level of less than 0.003 mW during a very lowleakage mode.33. The device of any of embodiments 1-32, wherein the logic device isoperative at a current of less than 2 mA during a transmit state.34. The device of any of embodiments 1-33, wherein the logic device isoperative at a power level of less than 5 mW during a transmit state.35. The device of any of embodiments 1-34, further comprising a casingof a biocompatible material, the communication unit and the processingunit housed with the casing.36. The device of embodiment 35, wherein the casing is sized to be lessthan 2 cm in any one dimension.37. The device of any of embodiments 35-36, wherein the casing is sizedto be less than 1 cm in at least one dimension.38. The device of any of embodiments 35-37, wherein the biocompatiblematerial of the casing is titanium or a biocompatible polymer.39. The device of any of embodiments 35-38, further comprising a skinpatch for attaching the casing to a skin surface of a patient.40. A system comprising:

an RF/ultrasound communication device of embodiment 20; and

one or more ultrasound communication devices of any of embodiments 1-39implantable within a body and capable of ultrasound communication withthe device of embodiment 20.

41. The system of embodiment 40, wherein the RF/ultrasound communicationdevice is worn on a skin surface of a body and the one or moreultrasound communication devices are implanted within the body.

42. The system of any of embodiments 40-41, further comprising an accesspoint device, including a communications interface operative to receiveand transmit radio frequency transmissions with the RF/ultrasoundcommunication device.

43. The system of any of embodiments 40-42, further comprising a one ormore sensing devices selected from the group consisting of a motionsensor, a gyroscope, an accelerometer, a cardiac rhythm monitor, a heartrate monitor, a pulse monitor, a blood pressure monitor, a glucosesensor, a drug pump monitor, a sleep sensor, a REM sleep durationsensor, a still camera, a video camera, a sensor for one or morebiomolecules, a sensor for one or more pharmaceutical agents orpharmaceutical formulation ingredients, a sensor for a dissolved gas orion, and a sensor for pH, ionic strength or osmolality; wherein eachsensing device is in communication with an ultrasound communicationdevice of the system.44. The system of any of embodiments 40-43, further comprising one ormore actuating devices selected from the group consisting of a drugpump, a heart stimulator, a heart pacemaker, a bone growth stimulator, adeep brain stimulator, a neurostimulator, and a neuromuscular electricalstimulator; wherein each actuating device is in communication with anultrasound communication device of the system.45. A method of controlling a plurality of networked medical devices,the method comprising the steps of:

(a) providing the system of any of embodiments 40-44 further comprisingone or more sensing devices and/or one or more actuating devices, eachin communication with an ultrasound communication device of the system;

(b) configuring the protocol stack and logic device of each ultrasoundcommunication device in the system;

(c) acquiring data from the one or more sensing devices and optionallyprocessing the data;

(d) optionally communicating the data using the RF/ultrasoundcommunication device, an access point, and the internet to a physician;

(e) optionally receiving reprogramming instructions using theRF/ultrasound communication device, access point, and internet;

(f) reconfiguring the protocol stack and logic device of one or moreselected ultrasound communication devices in the system in response tothe reprogramming instructions; and

(g) optionally causing one or more of said actuating devices to changetheir actuation state.

46. The method of embodiment 45, wherein the reprogramming instructionsinclude altering one or more of a data acquisition rate, a datatransmission rate, and a type of data sensed by one or more of saidsensing devices.

47. The method of any of embodiments 45-46, wherein the reprogramminginstructions include one or more of altering a parameter, a duty cycle,and a state of one or more of said actuating devices.

48. The method of any of embodiments 45-47, wherein the reprogramminginstructions include altering one or more of a dosage and a rate ofadministration of one or more agents.

49. The method of any of embodiments 45-48, wherein the reprogramminginstructions include altering an instruction to one or more of saidsensing devices or said actuating devices in response to a feedbackalgorithm.

50. The method of any of embodiments 45-49, wherein the reprogramminginstructions include altering an instruction to one or more of saidsensing devices or said actuating devices in response to a physiologicalor pathological state of a patient.

51. The method of any of embodiments 45-50, wherein the reprogramminginstructions include triggering a reading from one or more of saidsensing devices or said actuating devices and processing the reading.

52. The method of any of embodiments 45-52, wherein the reprogramminginstructions include altering an instruction to adjust at runtime a coreclock frequency according to a processing power requirement, select alow-power mode, provide an automatic wake-up, or power up or shut downinstruction.

DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood from the following detaileddescription taken in conjunction with the accompanying drawings inwhich:

FIG. 1 is a schematic illustration of an embodiment of an Internet ofMedical Things;

FIG. 2 is a schematic illustration of an Internet of Medical Thingsplatform hardware architecture;

FIG. 3A is a schematic illustration of an embodiment of an IoMT-mote;

FIG. 3B is a schematic illustration of an embodiment of an IoMT-patch;

FIG. 4 is a schematic illustration of an IoMT platform softwarearchitecture;

FIG. 5 is an illustration of an ultrasonic alpha-prototype node notincluding a preamplifier;

FIG. 6 is an illustration of ultrasonic transducers with and withoutcasing;

FIG. 7 is a schematic block diagram of an embodiment of an FPGA designincluding Tx and Rx chains with SPI, PPL and Register Manager modules;

FIG. 8 is a schematic block diagram of an embodiment of MCU firmwarearchitecture employing a KL03 MCU;

FIG. 9 is a schematic diagram of an embodiment of primitive blocks of aheart rate monitor;

FIG. 10 is an embodiment of a screenshot of a BLE app GUI;

FIG. 11 is a schematic illustration of an embodiment of a currentmeasurement setup;

FIG. 12 is a graph of attenuation in pork meat for 2.4 GHz RF, and for700 kHz ultrasonic waves as a function of propagation distance;

FIG. 13 is an illustration of an example of a measurement setup for aCC2650 device through pork meat using Faraday bags;

FIG. 14 is a graph of ultrasonic channel impulse response for (a) upperarm phantom and (b) thoracic phantom;

FIG. 15 is an illustration of an experiment setup employing an upper armphantom;

FIG. 16 is a graph of BER as a function of the transmission power (dBm)for a no-amp scenario in the upper arm phantom for code length in {1, 2,3, 4, 5} and frame length equal to 2 (top) and 1 (center), and for framelength in {1, 2, 3, 4, 5} and code length equal to 2 (bottom);

FIG. 17 is an illustration of an experiment setup for a thoracicphantom;

FIG. 18 is a graph of BER as a function of the transmission power in thethoracic phantom for code and frame length equal to 2 and differentvalue of amplification gain at the receiver;

FIG. 19 is an illustration of an experiment setup for pork meat scenarioalong 12 cm;

FIG. 20 is graph of PER for UsWB as a function of the transmission powerin the 12 cm meat setup for code and frame length in {1,2} (top); PER ofBLE in pork meat as a function of the transmission power for differentcommunication distances (center); PER of BLE and UsWB (code and framelength equal to 1) as a function of the transmission power in 12 cm porkmeat (bottom);

FIG. 21 is a graph of UsWB and BLE energy per bit (top) and networklifetime (bottom) as a function of the BER (left); UsWB and BLE energyper bit (top) and network lifetime (bottom) as a function of the BER in12 cm of pork meat (right); and

FIG. 22 is a schematic illustration of an overview of an implantablenode networking framework.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to embodiments of an Internet of MedicalThings (IoMT) platform with ultrasonic wireless connectivity that can beused as a base for building future IoT-ready medical implantable andwearable devices that communicate safely, reliably and with low-powerconsumption through body tissues using ultrasounds instead of RF-waves.Ultrasounds are mechanical waves that propagate in elastic media atfrequencies above the upper limit for human hearing, i.e., 20 kHz.Compared to RF-waves, ultrasounds have significantly lower absorption byhuman tissues (e.g., around 70 dB less attenuation for a 1 MHzultrasonic link compared to a 2.45 GHz RF link over 10 to 20 cm);therefore, lower transmission power is needed, and implantablebattery-powered devices can last longer and/or be smaller in size.Moreover, the medical experience of the last several decades hasdemonstrated that ultrasonic heat dissipation in tissues is minimalcompared to RF, and for this reason, the FDA also allows much higherintensity for ultrasonic waves (720 mW/cm²) in tissues as compared to RF(10 mW/cm²). By using ultrasounds for connecting medical implants,patients can benefit from implants that provide wireless telemetry,reprogrammability and continuous real-time monitoring while minimallyaffecting the battery lifetime of the device. This reduces the number ofsurgical procedures required to replace the implant. Real-time remotemonitoring applications can reduce in-office visits and hospitalization,leading to substantial savings in medical costs. Furthermore, low-powerultrasonic communications can enable advanced therapies that requirewireless reliable communication through tissues between multipleimplantable sensing and stimulating devices. From a security andreliability perspective, the ultrasonic communications cannot be easilyeavesdropped or jammed without physical contact. Additionally,ultrasounds eliminate electromagnetic compatibility concerns of acrowded RF spectrum. It is therefore safer and transparent to the RFspectrum management procedures of healthcare facilities.

The system includes a set of software-defined cross-layerfunctionalities tailored for networking ultrasonic wearable devices thatoffer real-time reconfigurability at different layers of the protocolstack, i.e., the physical (PHY), data link, network and applicationlayer. More specifically, the system encloses a set of PHY, data linkand network functionalities that can flexibly adapt to the applicationand system requirements, to optimally network information betweenultrasonic wearable devices. The system also offers real-timereconfiguration at the application layer to provide a flexible platformto develop medical applications. In particular, the system includessensor data processing applications running in nodes of a network thatcan be decomposed into primitive building blocks that can be arbitrarilyarranged to create new sensing applications to fit the userrequirements.

Embodiments of the system and method can employ aspects at differentlayers of the protocol stack to overcome limitations posed by thepropagation characteristics of ultrasonic waves in air. For example, twosignaling schemes, GMSK and orthogonal frequency-division multiplexing(OFDM), can be suitably used because of their high spectral efficiencyand resilience to multipath. Two different synchronization modes can bealternatively and suitably used for channels strongly affected bymultipath or by Doppler effect. Upper layer protocols andfunctionalities can be selected to address challenges posed by the longpropagation delays of ultrasounds in air that might prevent accuratetiming.

Ultrasounds are mechanical pressure waves that propagate through elasticmedia at frequencies above the upper limit for human hearing, i.e., 20kHz.

Attenuation.

Two main mechanisms contribute to ultrasound attenuation in tissues,i.e., absorption and scattering. An initial pressure P₀ decays at adistance dP(d)=P ₀ e ^(−αd)where α (in [Np·cm⁻¹]) is an amplitude attenuation coefficient thatcaptures all the effects that cause dissipation of energy from theultrasound wave. Parameter α depends on the carrier frequency throughα=af^(b), where f represents the carrier frequency (in MHz) and a (in[Np m⁻¹ MHz^(−b)]) and b are attenuation parameters characterizing thetissue.

Two mechanisms mainly contribute to acoustic attenuation in air, i.e.,spreading loss and absorption loss. The former includes sphericalspreading, i.e., the acoustic pressure falls off proportionally to thesurface area of a sphere. The latter is mainly related to atmosphericabsorption caused by the interaction of the acoustic wave with the gasmolecules of the atmosphere and is frequency, temperature, and humiditydependent.

For a signal at frequency f [Hz] over a transmission distance d [m], theattenuation can be expressed in [dB] asA _(dB)=20 log₁₀(d)+dα(f),where α(f) [dB/m] is the absorption coefficient, which increasesquadratically with the frequency, but also depends on the ambientatmospheric pressure, temperature, and the molar concentration or watervapor, i.e., humidity.

Propagation Speed.

Ultrasonic wave propagation is affected by propagation delays that areorders of magnitude higher than RF. The propagation speed of acousticwaves in biological tissues is approximately 1500 m/s, as compared to2×10⁸ m/s for RF waves.

The propagation speed of acoustic waves in air is approximately 343 m/sat a temperature of 20° C. and at atmospheric pressure of 101.325 kPa,as compared to 3×10⁸ m/s for RF electromagnetic waves. The speed ofsound in air increases with temperature and humidity, going from 331 m/sat a temperature of 0° C. and 10% relative humidity to 351 m/s at atemperature of 30° C. and 90% relative humidity.

Operating Frequency.

Considerations in determining the operating frequency are (i) thefrequency dependence of the attenuation coefficient, and (ii) thefrequency dependence of the beam spread of ultrasonic transducers (whichis inversely proportional to the ratio of the diameter of the radiatingsurface and the wavelength). Therefore, higher frequencies help keep thetransducer size small, but result in higher signal attenuation. Sincemost biomedical sensing applications require directional transducers,one needs to operate at the lowest possible frequencies compatible withsmall-size transducers and required signal bandwidth. For propagationdistances in the order of several cm. the operating frequency should notexceed 10 MHz.

Doppler Spreading.

Doppler spreading occurs as a result of Doppler shifts caused byrelative motion between source and receiver, and is proportional totheir relative velocity. Doppler spreading generates two differenteffects on signals: a simple frequency translation, and a continuousspreading of frequencies that generates intersymbol interference (ISI),thus causing degradation in the communication performance. Since thespeed of sound is several orders of magnitude lower than the speed ofelectromagnetic waves, the resulting Doppler effect is severe, even atrelatively low speeds.

Reflections and Scattering.

The human body is composed of different organs and tissues withdifferent sizes, densities and sound speeds. Therefore, it can bemodeled as an environment with pervasive presence of reflectors andscatterers. The direction and magnitude of the reflected wave depend onthe orientation of the boundary surface and on the acoustic impedance ofthe tissues, while scattered reflections occur when an acoustic waveencounters an object that is relatively small with respect to itswavelength or a tissue with an irregular surface. Consequently, thereceived signal is obtained as the sum of numerous attenuated, possiblydistorted, and delayed versions of the transmitted signal.

The on-body ultrasonic channel is composed of several interfaces betweenair and human body, and between air and on-body and near-body objects.Because of this inhomogeneous pattern, the on-body channel can bemodeled as an environment with pervasive presence of reflectors andscatterers. The direction and magnitude of the reflected wave depend onthe orientation of the boundary surface and on the acoustic impedance ofthe different media involved. Scattered reflections occur when anacoustic wave encounters an object that is relatively small with respectto its wavelength. (The acoustic impedance is defined as the productbetween the density of a medium p and the speed of sound in the mediumc.) Consequently, the received signal is obtained as the sum of numerousattenuated, possibly distorted, and delayed versions of the transmittedsignal.

Ultrasonic Transducers.

An ultrasonic transducer is a device that converts electrical signalsinto ultrasonic signals and vice versa. Ultrasonic transducers can becategorized into two main classes based on the physical mechanism thatenables the conversion, i.e., piezoelectric and electrostatictransducers. A piezoelectric transducer produces a mechanical vibrationthrough a thin piezoelectric element under an external voltagevariation, and produces a voltage variation under an external mechanicalvibration. In electrostatic transducers the fundamental mechanism is thevibration of a thin plate under electrostatic forces.

When sound passes across an interface between two materials, it is inpart transmitted and in part reflected. To maximize the acoustic energyradiated by the transducer, the acoustic impedance of the radiatingsurface should match the acoustic impedance of the propagation medium.Today, microelectro-mechanical (MEMS) technology has enabled thefabrication of microscopic piezoelectric and electrostatic transducers,i.e., so-called Micromachined Ultrasonic Transducers (MUTs). With MUTs,the acoustic impedance can be controlled to match the external medium bymanipulating the device geometry. This characteristic makes MUTssuitable for air-coupled applications.

When the operating frequency of the ultrasonic communications falls inthe near-ultrasonic frequency range, i.e., 15 to 17 kHz to 20 to 22 kHz,acoustic waves can be recorded and generated using components, such asmicrophones and speakers, which can be commercial off the shelf (COTS)components. Even though COTS components are often designed to operate alower frequencies, i.e., at 0-17 kHz, they can still sense and generate,albeit less efficiently, near-ultrasonic frequency waves. Since manycommercial devices such as smartphones, tablets and laptops amongothers, are equipped with audio interfaces, they can in someembodiments, support near-ultrasonic communications with no additionalhardware.

I. IOMT PLATFORM ARCHITECTURE

Embodiments of an IoMT platform provide a modular software and hardwarearchitecture to be used as a basis for future low-power IoMT-readywearable and implantable devices that communicate wirelessly throughultrasounds. Embodiments of the IoMT platform allow the ability to (i)remotely measure, store, and manage on the cloud vital physiologicalparameters of a patient measured by the implantable sensors (telemetry);(ii) remotely control actuators deployed in the body of the patient,e.g., stimulators, controlled drug pumps, and pacing devices; (iii)enable closed-loop feedback applications. For example, a smart coronarystent could detect potential clogs and allow the doctor to remotelymonitor the patient condition and automatically trigger injection ofdrugs that prevent artery re-occlusion. Furthermore, the ultrasonic IoMTplatform can also support implant-to-implant communication throughentirely intra-body communication links. This can enable closed-loopapplications where actuators perform an action (e.g., stimulate) basedon physiological data captured by sensors implanted elsewhere in thebody. For example, a smart neurostimulator can be triggered by a motionsensor or a heart rate sensor to anticipate an epileptic attack.

FIG. 1 shows an embodiment of a general application scenario enabled bythe IoMT platform, where a set of sensors and actuators, here IoMT-motes12, deployed inside the body 14 of a patient that communicate with eachother through inside-the-body ultrasonic links 16 (dotted lines), andalso with wearable devices, here IoMT-patches 18, deployed along or onthe body of the patient (dashed lines) 22. The IoMT-patches can enablecommunication from the intra-body network to an access point device 24,e.g., a smartphone or a gateway, through traditional radiofrequency-based technologies 26, e.g., BLE or 802.15.4/6LOWPAN. Theaccess point device connects the system to the user and to the Internet28 enabling remote monitoring, control and cloud storage on a server.

A. Hardware Architecture

The IoMT-mote and the IoMT-patch (IoMT-devices in general) are based onembodiments of an ultrasonic IoMT platform modular hardwarearchitecture, shown in FIG. 2. The core unit 40 of the node includes (i)reconfigurable logic device 42, such as a mm-size low-power fieldprogrammable gate array (FPGA), (to enable flexible hardwarereconfiguration in charge of executing physical layer protocols) and(ii) a micro controller unit (MCU) 44. Their combination offers hardwareand software reconfigurability with very small packaging and low energyconsumption. The miniaturized FPGA hosts the physical (PHY) layercommunication functionality. Reconfigurability at the physical layer isdesirable—implants have often a lifetime of 5 to 10 years at least,while wireless standard chipsets have a lifetime of 1.5 years and becomesoon outdated. The MCU is in charge of data processing and of executingsoftware-defined functionality to implement flexible and reconfigurableupper-layer protocols, e.g., non-time critical MAC functionality,network, transport and application. The ultrasonic interface 50 enablesultrasonic wireless connectivity for both the IoMT-motes and theIoMT-patches, and includes a receiver (Rx) and a transmitter (Tx) chain.The Rx chain includes a low-noise amplifier 52 and an analog-to-digitalconverter (ADC) 54 to amplify and digital-convert received signals,while the Tx chain embeds a digital-to-analog converter (DAC) 56 and apower amplifier (PA) 58 to analog-convert and amplify the digitalwaveform before transmission. Tx and Rx chains are in charge oftransmitting and receiving digital streams through the ultrasonictransducers 62. The hardware architecture also embeds an RF interface 64with an antenna to enable in-air RF wireless connectivity for example toconnect the IoMT-patches to an access point. The Plug-n-Sense (PnS) Unit66 includes a set of standard interfaces that allow the IoMT-mote toconnect with different sensors, e.g., pressure and glucose sensors, tothe ultrasonic IoMT platform according to the application and therapyrequirements. Also in some embodiments, the IoMT-patch can implementsensing capabilities for measuring vital biomedical parameters availableon the body surface, e.g., ECG signal or motion data. The PnS Unit canoffer both standard digital and analog interfaces to accommodatedifferent classes of sensors. The power unit 70 accommodates a battery72 and voltage regulation system for powering the device.

FIG. 3 shows embodiments of the IoMT-mote and the IoMT-patch includingthe logic, the battery, the ultrasonic transducer, and the casing. TheIoMT-devices can be miniaturized. In some embodiments, the dimensionscan be 1 cm×2 cm. In some embodiments, the IoMT-mote can be enclosed ina titanium biocompatible casing, The IoMT-patch can be enclosed in aplastic casing and attached to a disposable adhesive patch.

B. Software Architecture

In some embodiments, the IoMT platform can include a software-definedarchitecture designed to network IoMT-devices that encloses a set ofPHY, data link and network layer functionalities that can flexibly adaptto the application and system requirements to efficiently distributeinformation. The IoMT software framework can provide real-timereconfigurability at the application layer to provide a flexibleplatform to develop medical applications. In some embodiments, sensordata processing applications running in the nodes are decomposed intoprimitive building blocks that can be arbitrarily arranged to create newsensing applications that fit the application requirements. FIG. 4illustrates an embodiment of a high level description of an IoMTsoftware architecture. The FPGA 44 logic design implements the PHY layercommunication functionalities, as well as the interfaces, e.g., SPI andI2C, to connect the FPGA chip with the MCU 44 and the peripherals (DAC56, ADC 54). The MCU software design can be based on a real-timeoperating system (RTOS) and executes the upper layer communicationfunctionality and protocol, e.g., link layer (LL), Medium Access control(MAC), Network and Application layer. In some embodiments, the MCUsoftware design defines SPI and I2C interfaces to enable data exchangebetween the MCU and the peripherals (FPGA 44, RF interface 46 andsensors 66).

II. IOMT-MOTE DEVICE

Described herein are embodiments of a IoMT-mote device, which may alsobe termed an implantable device or node, that can be based on the IoMTplatform software and hardware architecture discussed above in SectionI.

A. Hardware Implementation

FIG. 5 shows an embodiment of a hardware implementation in a prototypestage, i.e., using development boards for each component connectedthrough wires. Circles highlight the main integrated circuit in eachdevelopment board. The ADC evaluation board is flipped for wiringconvenience, therefore the front side with ADC is shown in a bubbleabove. The ADC receives data directly from the Rx ultrasonic transducer.The FPGA outputs digital waveforms to the Tx ultrasonic transducers. TheFPGA is connected to the MCU and ADC evaluation board through SPIinterfaces as slave and master, respectively. (See FIG. 4.) In thissetup, the receiver preamplifier board, as well as the RF Interfaceboard are not included. In some embodiments, all the components can beintegrated into a printed circuit board enclosed in a biocompatible caseas shown in FIG. 3A.

1) Core Unit: The core unit of the node includes (i) a mm-size low-powerfield programmable gate array (FPGA) and (ii) a micro controller unit(MCU).

FPGA.

In one embodiment, a Lattice Semiconductor iCE40 Ultra is used, which isa commercially available small, low power, and integrated FPGA. Itoffers 4 k look-up-tables (LUTs) in a very small 36-ball wafer levelchip scale package (2.08×2.08 mm) with very low static current drain (71μA). The FPGA operates with 1.2 V and 3.3 V dual voltage for the coreand the digital input/output, respectively. The breakout evaluationboard that Lattice offers for the iCE40 Ultra is used, which providesthe FPGA with a clock of 12 MHz.

MCU.

The MCU is in charge of executing functionalities to coordinate thetransmission operation and implement upper-layer protocols. Mm-sizepackaging and low-power consumption are desirable requirements in thisembodiment. Therefore a Freescale Kinetis KL03 ultra-low-power MCU isused. The KL03 MCU is a 32-bit ARM Cortex-M0+ core in an ultra-smallchip-scale package 1.6×2.0 mm specifically designed to develop smart andminiaturized devices. The tiny packaging and low-energy functionalitiesmake Freescale Kinetis KL03 a suitable match for this embodiment. TheKL03 also embeds a 12-bit ADC with up to 818 kHz sampling frequency thatcan be used to interface the MCU with external analog sensing devices.For this embodiment, a FRDM-KL03Z, a breakout evaluation board for theKL03 MCU is used.

2) Ultrasonic Interface: The ultrasonic interface enables ultrasonicwireless connectivity through data converters, low-noise amplifiers(LNA), and custom ultrasonic transducers.

Ultrasonic Transducers.

The IoMT-mote embodiment embeds a miniaturized ultrasonic transducer togenerate and receive ultrasonic waves. The transducer operates around700 kHz, and is based on a thin-disk piezoelectric element that offersrelative large bandwidth, i.e., around 200 kHz, with no need for anybacking material that would increase the transducer size. Thepiezoelectric element is around 9.5 mm in diameter, and has a thicknessof about 3 mm. 700 kHz can be selected as an operating frequency becauseit offers a good tradeoff between attenuation of ultrasounds in tissue(increasing with frequency), thickness of the piezoelectric element(increasing with frequency), available bandwidth (increasing withfrequency), and radiation directivity (increasing with frequency). Adiameter of 9.5 mm is selected because it is a good tradeoff pointbetween size, conversion loss (increasing with smaller disks), anddirectionality (decreasing with smaller disks). In some embodiments,there can be 6 dB of conversion loss of the transducers betweentransmitting and the receiving transducers, when ideally no attenuationis introduced by the medium, e.g., short distance in water. Assuming theelectric-to-acoustic and acoustic-to-electric efficiency to be equal,the conversion efficiency can be obtained as half the measured loss. Inthe embodiments described, the disk is embedded in an epoxy waterproofcasing, which includes coupling layer, electrodes, and a micro-coaxialcable. In some embodiments, the IoMT-mote can embed the rawpiezoelectric disk together with the logic and the battery in a casing.FIG. 6 shows an embodiment of the ultrasonic transducer with casing, aswell as the piezoelectric element compared with a quarter for size.

ADC.

In some embodiments, the device can operate at 700 kHz centralfrequency, with a −3 dB bandwidth of about 200 kHz. In some embodiments,a sampling frequency of the ADC can be fixed around 2 MHz. In someembodiments, a small low-power data converter, e.g., a TI ADS7883commercially available from Texas Instrument (TI), can be used, whichsatisfies the sampling rate parameters. The ADC, e.g., the ADS7883, canbe connected to the FPGA through an SPI interface as slave peripheraland clocked by the FPGA that operates as SPI master. In someembodiments, the SPI connection uses three pins to output data throughSPI protocol, i.e., clock, enable, and data out. This reduces theconverter sizes compared to parallel converters, where samples areloaded in parallel requiring as many pins as the number of bits persample. Having fewer pins is useful when a limited number of pins isavailable on the FPGA, e.g., 36 in total. In some embodiments, the ADC,e.g., the ADS7883, can offer a power-down mode where current consumptionis as low as 1 1 μA, and TI offers breakout evaluation boards thatinclude fully functional circuit designs with voltage reference andamplification circuits, as well as I/O accessible via headers.

Since the ADC operates serially on 16-bit samples (12 information bitsand 4 control/padding bits), for a sampling rate of 2 MHz, the SPI linkoperates at 32 Mbit/s, which is achieved by feeding the SPI Master witha 32 MHz clock.

Driving the entire FPGA logic with an external 32 MHz clock rate iscertainly possible, but can be undesirable because it would lead tounnecessary high dynamic power consumption, which is proportional to thecircuit clock frequency and results from signal switching activity.Accordingly, an ultra-low power PLL, which is included in the iCE40Ultra FPGA (described further below), can be used, to internallysynthesize the 32 MHz clock from the 12 MHz clock on the FPGA evaluationboard to individually drive the SPI Master block. By using the PLL tosynthesize the high frequency clock signal, the rest of the logic can bedriven with the original lower-frequency external clock signal, e.g., 12MHz. Also, the PLL can be turned into low-power mode to minimize theenergy consumption when communication with the ADC and DAC is notneeded.

LNA.

In some embodiments, the ADC, e.g., the ADS7883 ADC, can accept aunipolar input ranging in 0 to V_(cc). A signal conditioning circuit canbe used to offset the input signal at the receiver from DC to V_(cc)/2.The signal conditioning circuit can be implemented using a low-noise,low-distortion and low power operational amplifier (e.g., TI OPA835)configured as an inverting gain of 1 that shifts the signal to thedesired DC offset of V_(cc)/2 and consumes as low as 250 μA when poweredon.

In some embodiments, to increase the receiver sensitivity and thereforebeing able to operate at lower transmission powers, a low noise andvariable gain amplifier (VGA) can be used before the signal conditioningcircuit. For example, the AD8338 VGA offers low current consumption,i.e., 3 mA, and a voltage controlled gain between 0 to 80 dB. Byreducing the transmission power, energy can be saved at the transmitter,but the power consumption is increased at the receiver to power thepreamplifier. Therefore, the use of the VGA can be applicationdependent.

Tx Chain.

In some embodiments, in the Tx chain, a low-power, low-complexity andlow-cost solution can be implemented that does not require a DAC toconvert digital waveforms to analog. Because of the impulsive nature ofthe UsWB transmission scheme, in some embodiments, the system cantransmit digital square pulses (0 to V_(cc)) from the digital output ofthe FPGA, with no need for analog conversion. The digital pulses can bedirectly fed into the transducer that filters out the out-of-bandfrequency components, and therefore shapes the square wave into a sinewave centered in 700 kHz. By avoiding the DAC, the size and energyconsumption can be reduced, as well as the complexity and cost of thedevice. In this implementation, a power amplifier is not used, since theoutput power of the FPGA output pin is sufficient to satisfy thecommunication link budget requirements.

3) Power Unit: In some embodiments, the power unit can be a commercialpower supply that offers adjustable voltage level, as well as onboardvoltage regulators that allow each board to be powered through USB. Insome embodiments, the power unit can accommodate a smallimplantable-grade battery with, e.g., 3.3 V nominal voltage. Alow-dropout (LDO) regulator (e.g., TI TLV716P) can be used to generatethe 3.3 V required to power the MCU. The other components can be poweredthrough the MCU pins that can output up to 25 mA, and allows poweringflexibility to reduce the energy consumption of the system, as discussedin Section II-B2 below. In some embodiments, the power unit can embedtwo integrated circuits that manage the human energy harvesting andultrasonic energy transferring functionalities. The former allows theharvesting of vibrational energy available in the body, e.g., heart beator human voice reverberations. The latter allows the collection ofenergy from ultrasonic waves transferred from an out-the-body ultrasonicsource.

4) Sensing and/or Actuating Unit Interface: In some embodiments, theimplantable node can include a flexible interface system to accommodatedifferent sensing or actuating units, e.g., pressure and glucose levelsensors, and actuating units, e.g., leads for electrical stimulations ormicro-needles. The implantable node board can employ small pin headerswhere different detachable and interchangeable boards, i.e., daughterboards, can be connected. Each daughter board can accommodate differentsensing or actuating units, making the implantable node a flexiblesensing and actuating medical platform operable with many applications.The communication between the implantable node main board and thedaughter boards can be handled by the MCU or the FPGA through serial orparallel connections. It will also be appreciated that a sensing and/oractuating unit can be hard wired to the implantable node.

Sensing units can include, for example and without limitation, a motionsensor, a gyroscope, an accelerometer, a cardiac rhythm monitor, a heartrate monitor, a pulse monitor, a blood pressure sensor, a glucosesensor, a drug pump monitor, a sleep sensor, a REM sleep durationsensor, a still camera, a video camera, a sensor for one or morebiomolecules, a sensor for one or more pharmaceutical agents orpharmaceutical formulation ingredients, a sensor for a dissolved gas orion, and a sensor for pH, ionic strength or osmolality. The sensor forone or more biomolecules can be a sensor for one or more peptides,oligopeptides, polypeptides, proteins, glycoproteins, antibodies,antigens, nucleic acids, nucleotides, oligonucleotides, polynucleotides,sugars, disaccharides, trisaccharides, oligosaccharides,polysaccharides, lipids, glycolipids, proteolipids, cytokines, hormones,neurotransmitters, metabolites, glycosaminoglycans, and proteoglycans.

Actuating units can include, for example and without limitation, a drugpump (such as an insulin pump), a heart stimulator (such as adefibrillator), a heart pacemaker, a bone growth stimulator, a deepbrain stimulator, a neurostimulator, an electrode or electrode array,and a neuromuscular electrical stimulator.

B. Software Implementation

As discussed in Section I-B above, the FPGA logic can be mainly incharge of implementing the PHY layer functionality, while the MCU runsthe MAC and LL functionality, IPv6 integration, as well as applicationlayer functionality, such as sensor data acquisition and reconfigurabledata processing operations. In some embodiments, a software-definedimplementation can be used for the UsWB transmission scheme andprotocol. UsWB is an impulse-based ultrasonic transmission and multipleaccess technique based on the idea of transmitting shortinformation-bearing carrierless ultrasonic pulses, following apseudo-random adaptive time-hopping pattern with a superimposedspreading code of adaptive length. Impulsive transmission andspread-spectrum encoding combat the effects of multipath and scatteringand introduce waveform diversity among interfering transmissions.

The implantable node software architecture can include asoftware-defined networking framework that encloses a set of PHY, datalink and network layer functionalities that can flexibly adapt to theapplication and system requirements to efficiently distributeinformation. The implantable node framework can also offer real-timereconfigurability at the application layer to provide a flexibleplatform to develop medical applications. In particular, sensor dataprocessing applications running in the nodes can be decomposed intoprimitive building blocks that can be arbitrarily arranged to create newsensing applications that fit user requirements. FIG. 22 shows ahigh-level overview of an embodiment of the framework. It can include(i) PHY layer functionalities, including modulation and synchronization,for impulsive transmissions, (ii) data link layer functionalitiesincluding forward error control and medium access control (MAC)protocols, (iii) network layer functionalities, e.g., IPv4 and IPv6support and content-centric networking, and (iv) application layerfunctionalities, i.e., reconfigurable sensing data processing and userinterface. In some embodiments, these functionalities can be split intotwo different processing units. The data link, networking andapplication layer functionalities can be run on the MCU, andcomputationally demanding operations can be offloaded to the FPGA.

The implantable node networking framework provides interoperability withthe Internet by defining an adaptation layer that integrates IPv4 andIPv6 protocol support. The adaptation layer includes a set offunctionalities that interface the traditional IP network layer with theimplantable node MAC layer through IP header compression and IP packetfragmentation functions optimized for ultrasonic networks. Standardprotocols, such as TCP or UDP, or custom protocols can be implemented ata transport layer.

In some embodiments, the implantable node software architecture can besplit between the FPGA and MCU. The FPGA logic design can implement thePHY layer communication functionalities, as well as the interfaces,e.g., SPI and I2C, to connect the FPGA chip with the MCU and theperipherals (DAC, ADC, memory and sensors). The MCU software design canbe based on a real-time operative system (RTOS) and can execute theupper layer communication functionalities and protocol. The MCU softwaredesign can also define interfaces, e.g., SPI and I2C, to enable dataexchange between the MCU and the peripherals (FPGA, DAC, ADC, memory andsensors).

In some embodiments, the MCU software architecture can implement theupper layer networking functionalities and protocols. The softwaredesign can be based on a real-time operating system (RTOS) that providesreal-time performance and at the same time can offer a small andconfigurable footprint. Specifically, the RTOS can in a resourceconstrained environment. The RTOS can offer low-power functionalities,and can support SPI and I2C drivers to enable communications with theexternal peripherals (FPGA, DAC, ADC, memory and sensors). The RTOS canintegrate the TCP/IP stack to enable the implantable node to supportinternet-of-things (IoT) applications. The RTOS can run applicationlayer processing related to sensing or actuating operations. A number ofcommercial or open source RTOSs can be used, such as FreeRTOS orμTasker.

1) FPGA Design: In some embodiments, the FPGA top-level module caninstantiate Tx and Rx chain blocks implementing the UsWB transmitter andreceiver, respectively, as well as the SPI, PLL and register managermodules. In some embodiments, the FPGA top-level module can instantiateTx and Rx chain blocks that implement the PHY layer communicationfunctionalities, a set of first-in-first-out (FIFO) memory queue blocks,and a phase-locked loop (PLL) block. The logic can be driven by anexternal system clock signal input to one of the FPGA's pin.

UsWB PHY layer assumes time divided in slots of duration T_(c), withslots organized in frames of duration T_(f)=NT_(c), where N is thenumber of slots per frame. Each user transmits one pulse per frame in aslot determined by a pseudo-random time-hopping sequence. Bits mappedinto pulses through pulse position modulation (PPM), i.e., a ‘0’ bit iscarried by a pulse delayed by a time δ with respect to the beginning ofthe slot, while a ‘1’ symbol begins with the slot. Since a single pulsemay collide with pulses transmitted by other users with a probabilitythat depends on the frame size N, UsWB also adopts a spreading codesscheme where each information bit is mapped with a pseudo-orthogonalcode of variable length, M. FIG. 7 shows a block diagram of anembodiment of the FPGA design implemented on the iCE40 Ultra.

Tx/Rx Chain.

The Tx and Rx chain blocks implement the transmitter and receiver PHYlayer functionalities, respectively. This block gets as input a streamof bytes coming from the MCU though SPI, and outputs the PHY digitalwaveforms representing the modulated bits. The digital waveforms arethen passed to the DAC through SPI, digital-to-analog converted,amplified by the PA, and then transmitted from the ultrasonictransducers.

On the receiver side, the signal captured by the receiver ultrasonictransducers is first amplified by the LNA and then analog-to-digitalconverted by the ADC. The digital waveforms are input through SPI to theRx chain. This block can perform on the input waveforms digital signalprocessing operations such synchronization, channel estimation, anddemodulation. The output of this block is a stream of bytes that canthen be passed to the MCU via SPI.

Both the Tx chain and the Rx chain can run computationally complexoperations, e.g., correlations, fast-Fourier transforms (FFTs), ordigital filtering, among others, which are needed to implement PHY layerfunctionalities.

Tx Chain Design.

In some embodiments, the Tx chain can receive as input a stream of bytescoming from the MCU through the SPI Slave module, and outputs the PHYdigital waveforms representing the modulated bits. The digital waveformsare then transmitted to the ultrasonic transducer that converts theelectrical signal to ultrasonic signal and radiates it in thecommunication channel.

Raw information bits from the host are received at the Tx controller,which coordinates the PHY layer operations implemented by the otherblocks of the chain. The UsWB packet is then serialized, i.e., convertedinto a sequence of bits, and forwarded to the next module in the chain,i.e., Symbol Mapping. In the Symbol Mapping block the information bitsare mapped into {−1,1} binary symbols. The binary symbols are thenspread in chips by the Spreading Code module following a pseudo-randomspreading code. For each symbol, this block outputs M chips in {−1,1}.Chips are then forwarded to the Time-Hopping module that spreads them intime according to the selected time-hopping pattern. The time-hoppingpattern is generated locally using a Linear Feedback Shifter Register(LFSR) module. Finally, the Pulse Shaping module maps the incoming chipsto position-modulated pulses. The output is a train ofposition-modulated pulses following a predefined time-hopping pattern.Each pulse consists of three cycles of a 700 kHz square wave. A longerelectrical excitation gives higher output pressure because of theresonant operation of the transducers. However, longer pulses lower thedata rate. In some embodiments, three cycles can provide a goodcompromise between data rate and ultrasonic generation efficiency. Insome embodiments, each packet is preceded by two preambles. The firstpreamble consists of 64 cycles of a 700 kHz sine wave and it is used atthe receiver for packet detection, i.e., coarse synchronization. Thesecond preamble consists of a train of three pulses properly spaced intime, and it is used for achieving time-hopping synchronization, i.e.,fine synchronization.

Rx Chain Design.

In some embodiments, the receiver chain can implement the receiver UsWBPHY layer functionalities. The received ultrasonic signal is convertedto an electrical signal by the Rx transducer. The signal is amplified bythe LNA, and analog-to-digital converted by the ADC. Then, the receiverchain in the FPGA processes the digital waveform acquired through theSPI Master module. The receiver chain outputs a binary streamrepresenting the received decoded data, which are delivered to the MCUthrough the SPI Slave module. The Rx controller coordinates thePHY-layer processing of the received digital waveform. In someembodiments, the Rx controller can trigger the start of the PHY layerprocessing when synchronization is achieved, and make the decision ofthe received bits based on the output of the PHY layer processingblocks. The Rx controller can also be in charge of switching the ADC infrom power-down mode to power-up, and vice versa. The preamble detectorsinclude a packet detector and a time-hopping synchronization block. Theformer enables coarse synchronization by identifying an incoming packetusing an energy collection approach, which aims to detect the sine wavepreamble. The latter identifies the exact start point of thetime-hopping frame by correlating the received signal with a local copyof the transmitted pulse-train preamble. After synchronization isachieved, the time-hopping deframer jumps from frame to frame and feedsto the pulse correlator block only the time slots in which a pulse isexpected according to the time-hopping sequence in use. The time-hoppingsequence can be generated using a linear feedback shift register (LFSR)module that uses the same seed as the LFSR of the transmitting node. Thepulse correlator correlates and integrates the signal in each time slotand outputs a positive value for a slot containing a ‘1’ symbol, and anegative value for a slot containing a ‘−1’ symbol. The correlationoutput goes into the code despreader, which inverts the spreadingoperation by weighting the correlation output with the spreading codeoriginally used at the transmitter and summing these over the spreadingcode length. Based on the result of the despreading operation, the Rxcontroller makes a decision on the received bits. If the resulting sumis positive a 0-bit is received, otherwise a 1-bit is received.

Register Manager.

In some embodiments, a register manager can be in charge of storing androuting the configuration parameters written by the LL module running onthe MCU on a pool of setting registers implemented on the FPGA. Throughthese setting registers, one can reconfigure key parameters of the PHYlayer transmission scheme (i.e., frame and code length, among others).Whenever the driver reconfigures any parameter, the register managerstores the received data in the desired register and routes thisparameter to the destination module. This block enables real-timereconfiguration thus enhancing the transceiver flexibility. Thecommunication system can allow real-time reconfiguration of severalparameters, i.e., spreading code and spreading code length, time-hoppingframe length and time-hopping sequence, packet payload size, and lengthof the preambles.

SPI Module.

In some embodiments, the FPGA can include a configurable serialperipheral interface module. For example, the iCE40 Ultra FPGA has twoSPI hardened, i.e., already fabricated in the FPGA, IP cores. Thehardened cores are accessible through a system bus that providesconnectivity between FPGA user logic and the hardened IP blocks. Theuser can configure the cores to operate as master or slave, and canconfigure the SPI communication settings, e.g., data rate, clockpolarity and clock phase, among others. In some embodiments, the SPIinterfaces enable communication with the external peripherals and theMCU. In some embodiments, one hardened SPI core can be configured asslave, and one as master. The SPI Slave block is driven by the SPIMaster module of the MCU. This SPI link is used to pass the data to betransmitted to the FPGA, and to read the received data from the FPGA.Moreover, the MCU can use this serial link to deliver to the registermanager PHY layer parameters. The data rate on this link needs to begreater than the PHY layer data rate, such that the PHY Tx chain isalways backlogged with byte to transmit. In some embodiments, a 1 MHzSPI clock can be used. The SPI Master block can drive the communicationwith the ADC. For example, the SPI Master can trigger the samplingoperations on the ADC, and read back the sampled digital waveform. Asdiscussed in Section II-A2 above, to support 2 MHz sampling rate, theSPI Master link can be clocked at 32 MHz.

FIFOs.

In some embodiments, FIFO blocks can implement first-in-first-out memoryqueues that allow the storage and retrieval of ordered data. In oneembodiment, FIFO blocks can buffer data coming in and out of the FPGAfrom and to the external peripherals and the MCU, before being processedby the functional logic. FIFOs can also be used to handle multi-clockdomain data exchange, i.e., data flowing between logics driven by clocksignals with different frequencies.

PLL Module.

In some embodiments, the FPGA can include a Phase Locked Loop (PLL)module to provide a variety of user-synthesizable clock frequencies,along with custom phase delays, to support multi-clock domain designs.For example, the iCE40 Ultra FPGA includes an ultra-low power PhaseLocked Loop. The PLL can be used to internally synthesize the 32 MHzclock signal to individually drive the SPI Master block to minimizedynamic power consumption, which is proportional to the circuit clockfrequency. The PLL module can be shut down when communication with theADC is not needed to minimize the energy consumption.

FPGA Resource Utilization.

The FPGA includes programmable logic blocks (PLBs) that can beprogrammed to perform logic and arithmetic functions. Table I reportsthe FPGA resource utilization of the iCE40 device for the modulesdiscussed above in terms of programmable logic blocks (PLBs), andresource percentage. Each PLB includes eight interconnected logic cells(LC), and each LC contains one look-up table (LUT) and one register. Insome embodiments, the ICE40 Ultra FPGA contains 440 PLBs, i.e., 3, 520LC.

TABLE I Resource occupation of the logic implemented on the on the FPGA.Module PLBs % SPI Slave 61/440 14% Tx Logic 44/440 10% SPI Master 82/44018% Rx Logic 252/440  57% Tot 439/440  99%

The receiver logic occupies more than 50% of the available resources onthe FPGA. To bring down the total FPGA utilization below 100%, thesynchronization process can be simplified and optimized. In particular,the correlator templates used for synchronization can be square-shapedwaveforms of amplitude ‘−1’ and ‘1’, instead of sine wave templateswhich match the received signal. As a consequence, the template can beimplemented using 2-bit coefficients instead of 12-bit coefficients(same size as the input).

2) Core MCU Firmware: In some embodiments, the MCU software architecturecan be implemented on a real-time operating system (RTOS) to ease thedevelopment of complex software functionalities, e.g., timers andinterrupts for sensing and transmitting data. In one embodiment, anμTasker embedded RTOS was implemented, which can run in a resourceconstrained environment such as the Freescale KL03 MCU and offerssupport to the MCU low-power functionalities. μTasker is suited forembedded applications where tight control over resources is desired.FIG. 8 shows the firmware architecture implemented on the KL03 MCU. Inone embodiment of an application scenario, the application layer cantrigger a reading through the PnS interface from a digital or analogsensor. The sensor reading is then processed by the reconfigurable dataprocessing functionalities and passed to the LL protocol module fortransmission. The LL packet is passed to the FPGA driver module thattransmits the data to the FPGA through the SPI Master interface. Inparallel, the energy manager module can be in charge of switchingbetween different energy states to minimize the system energyconsumption.

Link Layer.

In some embodiments the UsWB Link Layer (LL) protocol can be in chargeof managing the data transmission over the UsWB PHY layer interface. Theconnection is established through an advertising process initiated by afirst node, i.e., the slave, which transmits periodically advertisingpackets on an advertising channels. The advertising channel isimplemented using a common and known-a-priori time-hopping sequence andspreading code. Data channels are implemented using unique and privatetime-hopping sequences and spreading code pairs shared between the twocommunicating nodes. The time interval between advertising packets canbe a fixed delay plus a random delay that reduces the possibility ofcollisions between advertisements of different devices. The advertisinginterval can be selected to find a compromise between energy consumptionand delivery delay. A long interval allows saving of power, but at thesame time significantly slows down the data exchange operations.

A second node, i.e., the master, scans the advertising control channel,and upon receiving an advertising packet, sends a connection request tothe slave and they agree on a connection interval between connectionevents in which the two nodes exchange data periodically. During aconnection event, both the slave and the master wake up, and the slavetransmits a data packet. Since the sleep clocks of the slave might driftaway from the sleep clock of the master, the slave starts listening onthe radio channel slightly before the agreed connection interval.

In some embodiments, the UsWB LL packet can include a 2-byte header, a3-byte CRC, and a variable size payload between 0 and 32 bytes. Theheader can include a 2-bit packet type field, i.e., advertising,connection request and data packet, 5-bit payload length, 3-bit Txaddress, 3-bit Rx address, 1-bit SN (sequence number), 1-bit NESN (nextexpected sequence number) and 1-bit MD (more data). The LL packet can bepreceded by the two synchronization preambles used for coarse and finesynchronization. The connection can use a stop-and-wait flow controlmechanism based on cumulative acknowledgments, with error recoverycapabilities as used in BLE LL protocols. The SN bit identifies thepacket, while the NESN indicates the next expected packet from the otherdevice. If a device successfully receives a data packet, it incrementsthe NESN of its next packet, serving as an acknowledgment. Otherwise,the receiving device retransmits the last transmitted packet, whichserves as a negative acknowledgment. A More Data (MD) bit indicates thatthe device has more data to send in the same connection event.

In some embodiments, the link layer can also implement driverfunctionalities for the for the UsWB transceiver implemented on the FPGAthat allows initializing the transceiver, configuring PHY layerparameters and triggering the transmitting and receiving operations.When data needs to be transmitted or received, the MCU can enable theFPGA operations, configure parameters such as code and frame length,among others, and pass the data to be transmitted or wait for thereceived data. This data exchange can be done through a SPI link betweenthe MCU (master) and FPGA (slave), and the register manager on the FPGAcan be in charge of storing and using the information received.

Application Layer.

In some embodiments, at the application layer, the MCU firmware canimplement the Plug-n-Sense (PnS) software module that allows theIoMT-mote to connect with different sensing devices. The PnS module caninclude a digital interface based on I2C/SPI Master interfaces that candirectly connect to sensors with digital output, as well as an analoginterface based on the 12-bit embedded ADC that can sample anddigital-convert the output of analog sensors. Data coming from the PnSmodule are then processed by the reconfigurable and modular dataprocessing module implemented in the MCU. Each sensor data is mappedinto a content object and advertised to make it reachable from theIoMT-patch. The IoMT-patch maps the content object to the LL address ofthe IoMT-mote generating the object, and therefore retrieves theinformation whenever needed. Application layer data can be encryptedend-to-end using a streamlined implementation of the Advanced EncryptionStandard (AES) based on a 128 bit key exchanged during paring betweentwo devices.

In some embodiments, the data processing module can be based ondecomposing the data processing applications running in the IoMT-moteinto primitive blocks, and offering real-time reconfigurability at theapplication layer. The processing application can include a sequence ofbasic operations that are executed on the sensed data to extract desiredmedical parameters. Real-time modular reconfiguration allows newprocessing functions to be wirelessly transmitted and installed on theIoMT-platform at runtime, such that new medical parameters can beextracted from the raw data coming from a sensor device, whilemaximizing code reusability. Defining new applications can includespecifying inputs, a chain of primitive blocks, and outputs. An input isthe digital or the analog interface of the PnS module, thus the sensordevice attached to it, e.g., an electrocardiogram (ECG). An output canbe either the local memory for storing a measured parameter, or atransmission for sending a measured parameter to another IoMT-mote orIoMT-patch.

Based on this modular approach, applications can be represented bychains of binary sequences, i.e., keys. Each primitive function ismapped to a binary key. A concatenation of keys represents aconcatenation of operations, and therefore represents an application.The IoMT-mote feeds these keys into a finite state machine (FSM) whereeach state represents a primitive block function. By parsing theconsecutive function keys, the FSM transitions from state to state,processing inputs and producing outputs. In one example, an ECG-basedapplication measures the heart rate from a single electrode ECG signalcoming from the PnS interface. FIG. 9 shows a template signal with fivelabeled characteristic waveforms that correspond to electrical eventsduring one heartbeat, and present the simplified primitive blocksequences of the heart rate detector. The application measures the heartrate in beats-per-minute (bpm) by dividing 60 for the average of the RRinterval duration, i.e., distance between two consecutive R waveforms inthe trace.

A variety of sensor devices can be used, for example and withoutlimitation, a motion sensor, a gyroscope, an accelerometer, a cardiacrhythm monitor, a heart rate monitor, a pulse monitor, a blood pressuremonitor, a glucose sensor, a drug pump monitor, a sleep sensor, a REMsleep duration sensor, a still camera, a video camera, a sensor for oneor more biomolecules, a sensor for one or more pharmaceutical agents orpharmaceutical formulation ingredients, a sensor for a dissolved gas orion, and a sensor for pH, ionic strength or osmolality. Similarly, avariety of actuating devices can be used, for example and withoutlimitation, a drug pump, a heart stimulator, a heart pacemaker, a bonegrowth stimulator, a deep brain stimulator, a neurostimulator, and aneuromuscular electrical stimulator.

Energy Manager.

By leveraging μTasker RTOS primitives to enter and exit the KL03 MCUpower modes through interrupts generated by timers or external pins,software functionalities can be implemented to minimize the systemenergy consumption. In some embodiments, an energy management module canbe provided to do one or more of the following: (i) adjust at runtimethe core clock frequency according to the processing power required,(ii) select at runtime the low-power mode according to the applicationrequirements, (iii) implement automatic wake-up functionalities, and(iv) power up and shut down other components in the system to furtherreduce the system power consumption.

In some embodiments, in RUN mode the MCU operates at its maximumperformance and consumes, in one example, around 6.6 mA at 48 MHz. Everytime there are no tasks scheduled, the μTasker RTOS switchesautomatically to a low-power mode. By default, the MCU goes into WAITmode where all the peripherals function while the core is in Sleep mode,reducing the current drawn to 1 to 1.4 mA. As soon as a task isscheduled, an internal interrupt brings the MCU back to RUN mode. Whenless processing power is needed in RUN mode, e.g., when the MCU justreads and stores sensed information, the clock frequency can be reducedto lower the power consumption. For example, the MCU draws 1.8 mA and 1mA when under-clocking the system to 3 MHz in RUN and WAIT mode,respectively. In STOP mode, the MCU goes to deep sleep and all theperipheral clocks are stopped and the chip goes static state bringingthe current drawn down to 160 μA. In VLPS mode more peripheral are putto sleep and the current drawn is further reduced to 2.2 μA. In STOP andVLPS mode the nested vectored interrupt controller (NVIC) is disabled,and therefore the scheduler interrupts do not awaken the MCU. Instead,an asynchronous wake-up interrupt controller (AWIC) can be used to wakeup from timers or pin interrupts. Finally, in very-low-leakage stop(VLLS) mode, all the peripherals including the RAM are shut off,bringing the current drawn down to 0.6 μA. In VLLS1 mode the processorcan be awakened using a low-leakage wakeup unit (LLWU) that enablestimers, e.g., the LPTMR clocked by the low-power oscillator (LPO), to beprogrammed as wakeup sources.

To reduce the energy consumption of the entire system when idle, theenergy manager module can be in charge of powering up the systemcomponents only when needed. For example, the ADC is used only when thedevice is receiving; the FPGA running the PHY layer functionalities canbe used only when information has to be transmitted or received. In someembodiments, with the MCU in VLLS1 mode and the rest of the systempowered down, the device can consume less than 1 μA when not in use.

III. IOMT-PATCH DEVICE

The IoMT-patch device, which may also be termed a wearable device or agateway device or node, is deployed along a body to bridge theintra-body network of implantable node with the external world. TheIoMT-patch devices can also accommodate sensing capabilities ifrequired, e.g., electrocardiogram leads.

The IoMT-patch device hardware design can be similar to the IoMT-motedevice hardware design except for a few different components. TheIoMT-patch device can be a flexible sensing/processing/networkingplatform with a small and compact form factor, e.g., no more than twocentimeters per side in some embodiments, that can offer low energyconsumption, and that communicates wirelessly through ultrasounds andRF. The gateway node can be packaged such to offer a slim form factorthat can be attached to stick-on skin patches.

The hardware architecture of the IoMT-patch device can be similar to oneof the IoMT-mote device discussed above. The hardware design of theIoMT-patch device can be based on mm-sized and low-power fieldprogrammable gate arrays (FPGAs) or/and microcontroller units (MCUs)that offer hardware and software reprogrammability in small packages andlow energy consumption. The IoMT-patch device can optionally offersensing capabilities for measuring biomedical parameters measurable onthe body surface, e.g., ECG signals. The communication throughultrasounds, both with the IoMT-mote device in body tissues and with anaccess point node in air, can be done by using miniaturizedpiezoelectric transducers. For example, in some embodiments, theIoMT-patch device can embed two arrays of miniaturized ultrasonictransducers that offer high integration, as well as focusing andbeamforming capabilities that enhance the ultrasonic propagation in bodytissues and in air. The two arrays are differently coupled with theexternal medium to support communication in air and in body tissues,respectively. The IoMT-patch device also can embed a low-power RFtransceiver that enables communication via RF with the access pointnode. The IoMT-patch device is powered by a small and thin rechargeablebattery that can be recharged after detaching the device from the body.The IoMT-patch device can also provide human energy harvesting orultrasonic wireless energy transfer functionalities that help prolongingthe device battery life.

The communication interface enables ultrasonic wireless connectivitythrough data converters, power and low noise amplifiers, andtransducers. In some embodiments, the communication interface caninclude two receiver (Rx) and two transmitter (Tx) chains. The Rx chainscan include a low-noise amplifier and an analog-to-digital converter(ADC) to amplify and digital-convert the received signals. The Tx chaincan include a digital-to-analog converter (DAC) and a power amplifier toanalog-convert and amplify the digital waveforms before transmission. Txand Rx chains can be in charge to transmit and receive data through theultrasonic transducers. The first Tx/Rx chain pair is used for thein-tissue communication with the IoMT-motes, while the second Tx/Rxchain pair is used for the in-air communication with access point nodes.The communication between the core unit and the communication interfacecan be performed through serial or parallel communications.

The IoMT-patch devices can also embed a low-power RF transceiver thatenables communication via RF with access point nodes. In someembodiments, the RF chip can operate in the industrial, scientific andmedical (ISM) radio band as well as in the Medical Implant CommunicationService (MICS) band. The RF chip can implement wireless short range orlocal area network communication standards, such as Bluetooth, Wi-Fi orZigBee, as well as proprietary communication schemes and protocols.

The IoMT-patch device includes a power unit that can accommodate abattery element to power the device. The power unit of the IoMT-patchdevice can also embed a ultrasonic power transmission unit to wirelesslytransfer ultrasonic energy to the implantable nodes.

In some embodiments, an IoMT-patch device can be based on the samehardware and software implementation of the IoMT-mote device presentedabove in Section II, with the exception of the KL03 MCU, which can bereplaced with a wireless MCU that embeds the RF interface required inthe IoMT-patch to bridge the on-body system with the access point. Insome embodiments, an access point device can include a multi-platformsmartphone app that communicates via BLE with the IoMT-patch and givesthe user direct access to the sensed data. In some embodiments, anaccess point device can include a 6LOWPAN edge router implemented on atraditional computer or on single-board computer, e.g., Raspberry Pi,that enables IPv6 connectivity and allows direct data delivery to thecloud. In the following, an IoMT-patch implementation is described,focusing on the modules that differ from the IoMT-mote implementationdescribed above.

A. MCU and RF Interface

In some embodiments, the IoMT-patch can embed a wireless MCU, such as TICC2650 BLE MCU, that coordinates transmissions over the ultra-sonicinterface, as discussed in Section II-A1, and transmissions over the RFinterface, and implements upper layer protocols to interface the systemwith the access point device, e.g., a smartphone or the a 6LoWPAN edgerouter. The TI CC2650 MCU is a commercially available low power (between6 mA and 9 mA in Tx/Rx mode) and small (down to 4×4 mm) 2.4 GHz wirelessMCU that can operate in energy constrained systems powered by small coincell batteries. The CC2650 device contains a 32-bit ARM Cortex-M3processor running at up to 48 MHz that implements upper layers of theBLE protocol stack, as well as user defined functionalities. A secondarylow-power ARM Cortex-M0 processor is in charge of lower-level BLEfunctionalities and is interfaced with the embedded RF transceiver. Forone embodiment, the SmartRF development kit provided by the vendor wasused, which includes all the hardware and software tools needed to testthe radio performance and implement software operations

B. Software Implementation

In some embodiments, two different firmwares for the wireless MCU, e.g.,the TI CC2650, can be implemented. In some embodiments, a BLE-enabledfirmware based on TI-RTOS that implements BLE functionalities forconnecting the patch to the BLE access point, e.g., a smartphone. Insome embodiments, a IPv6-enabled firmware, such as that based on theContiki operating system that offers 6LoWPAN capability for IPv6 supportand connects to the 6LoWPAN edge router. Alternatively, asingle-solution RTOS that support both BLE and 6LoWPAN could be used. ABLE-enabled access point can be implemented through a multi-platformsmartphone app that collects sensed data and presents them to the userand a 6LoWPAN edge router example running on a Raspberry Pi that collectthe data and publish them on a cloud service via MQ Telemetry Transport(MQTT) protocol.

1) BLE-enabled Firmware: For the BLE-enabled firmware, in someembodiments, the RTOS from TI can be used, which offers preconfiguredand easy to use drivers for accessing the system peripheral, e.g.,SPI/I2C, managing the RF interface and provides easy access to the BLEprotocol stack library available on the device, as well as control ofthe power management of the device. The BLE interface can implementfunctionalities for establishing the connection between the IoMT-patchand the BLE access point and exchange of data between the two devices.The connection operations can be managed by the Generic Access Profile(GAP) layer of BLE. The connection can be established through anadvertising process initiated by the slave, i.e., the IoMT-patch, whichtransmits periodically advertising packets on three control channels. Insome embodiments, the advertising time can be set to 300 ms which is agood tradeoff between energy consumption and user experience. A longinterval allows saving power, but at the same time significantly slowsdown the connection operations. When the master, i.e., the BLE accesspoint, receives an advertising packet, it sends a connection request tothe slave and they agree on a connection interval between connectionevents in which the two nodes exchange data periodically. In someembodiments, the connection interval can be set to 2 s. When no moredata needs to be exchanged the connection is closed and the slave goesback to advertising mode.

In some embodiments, data exchange between connected devices can bemanaged by the General Attribute (GATT) layer of the BLE protocol stack,and data can be exchanged in form of characteristics. Characteristicscan be grouped in services, and services can be grouped in profiles. Forexample, in this implementation, consider a heart rate profile, whichincludes a Heart Rate Service and a Device Information Service, andcontains a Heart Rate Measurement that the access point wants toretrieve from the IoMT-patch. In the background, the IoMT-patchinitializes the ultrasonic intra-body communication to retrieve theheart rate measurement from the IoMT-motes. Each BLE characteristiccorresponds to one content object that is mapped to the LL address ofthe IoMT-mote that offers the object. During the over-the-air dataexchange, the communication is hard to eavesdrop because of thefrequency-hopping scheme adopted by the BLE physical layer. Moreover,the GATT layer can offer data protection through end-to-end encryption,authentication and authorization processes.

2) BLE-enabled Access Point: In some embodiments, a smartphone app canbe based on the Qt framework, which offers a set of easy-to-uselibraries to develop multiplatform application and user interfaces. Forexample, in some embodiments, the app can implement a simple BLE heartlistener that scans for BLE devices, connects to the Heart Rate servicerunning on the IoMT-patch and retrieves and presents to the user theheart rate measurement. The app can use the Qt BLE API that provide highlevel access to BLE drivers available on different platform. CurrentlyQt BLE API supports Android, iOS, Linux (BlueZ 4.x/5.x) and OS X. FIG.10 shows two example screenshots of an app graphic user interface (GUI)compiled for Android. Through the GUI the user can trigger a readingfrom the IoMT-patch and visualize the heart rate measurement.

3) IPv6-enabled Firmware: In some embodiments, for the IPv6-enabledfirmware, the Contiki OS can be used, which is designed for low-powerwireless Internet of Things devices. Contiki supports the 6LoWPANstandard, which offers encapsulation and header compression mechanismsthat allow IPv6 packets to be sent and received over IEEE 802.15.4 basedwireless mesh network networks. Using 6LoWPAN, the IoMT-patch can haveits own IPv6 address, allowing it to connect directly to the Internetusing open standards. An edge router, i.e., a gateway between the6LoWPAN mesh and Internet, can be used to provide a conversion between6LoWPAN and standard IP header. In some embodiments, the IoMT-patch canbe configured as a Message Queue Telemetry Transport (MQTT) client thatperiodically reads data from the IoMT-mote through the ultrasonicinterface, and publishes sensor readings to an MQTT broker, i.e., theserver responsible for distributing messages. The MQTT client module canbe responsible for opening the connection with the MQTT broker throughan IPv6 address, authenticating the application, and publishing newcontent when available. As an example, the device can be set up topublish readings to IBM Watson IoT Platform quick start service andvisualize the sensor readings together with the device uptime in secondsand the message sequence number.

4) 6LOWPAN Edge Router: An edge router, i.e., a gateway between the6LoWPAN mesh and Internet, can be used to provide a conversion between6LoWPAN and standard IPv6 header. In some embodiments, the edge routercan be implemented using the CETIC 6LBR 6LoWPAN Border Router solution.The 6LBR is deployment-ready and can be easily configured tointerconnect 802.15.4/6LoWPAN networks with an existing IPv6 network.The 6LBR can be run on, for example, a Raspberry Pi connected with an TICC2531 that provide the 802.15.4 radio interface, and with the Internetthrough the Ethernet interface.

The IoMT architecture platform and wirelessly networked systems ofimplantable and wearable medical devices endowed with sensors andactuators as described herein can be used for many therapies. Theplatform and devices can be used with artificial pancreases, i.e.,implanted continuous glucose monitors wirelessly interconnected withadaptive insulin pumps, for many type-1 diabetic patients. Post-surgerysensors can be used to detect changes in the microenvironment involvedwith the surgical procedure (pressure, pH, white cells concentration,LDH enzyme) to prevent infections or ischemias caused by tissueperfusion. Other applications include functional electrical stimulation,a type of neurostimulation to restore motion in people with disabilitiesby injecting electrical currents to activate nerves innervatingextremities affected by paralysis. Neurostimulators can be composed ofseveral miniaturized standalone stimulation devices that attach todifferent groups of neurons and wirelessly cooperate with each other tomodulate the electrical signaling patterns to restore the healthy statesof targeted organs and functions. Distributed pacemakers can includesensing and pacing devices implanted in the heart chamber connectedwirelessly with each other to enable advanced cardiac resynchronizationtherapy.

The sensor and/or actuating unit can employ a variety of sensors tosense biological parameters or actuators to actuate biological ormedical procedures.

In some embodiments, a sensor can comprise a motion sensor, a gyroscope,an accelerometer, a cardiac rhythm monitor, a heart rate monitor, apulse monitor, a blood pressure sensor, a glucose sensor, a drug pumpmonitor, a sleep sensor, a REM sleep duration sensor, a still camera, avideo camera, a sensor for one or more biomolecules, a sensor for one ormore pharmaceutical agents or pharmaceutical formulation ingredients, asensor for a dissolved gas or ion, or a sensor for pH, ionic strength orosmolality.

In some embodiments, the sensor for one or more biomolecules cancomprise a sensor for one or more peptides, oligopeptides, polypeptides,proteins, glycoproteins, antibodies, antigens, nucleic acids,nucleotides, oligonucleotides, polynucleotides, sugars, disaccharides,trisaccharides, oligosaccharides, polysaccharides, lipids, glycolipids,proteolipids, cytokines, hormones, neurotransmitters, metabolites,glycosaminoglycans, and proteoglycans.

A motion sensor can determine vibration, position, velocity, andacceleration by any active or passive means known in the art, such as byemitting and receiving infrared, microwave and/or ultrasonic radiations.

A gyroscope can allow the calculation of orientation and rotation, whilean accelerometer can measure non-gravitational acceleration. A gyroscopeand an accelerometer can be used separately, or they can be combined tocreate an inertial measurement unit to provide exact information onorientation, position, and velocity.

A cardiac rhythm monitor can detect abnormal or irregular heart rhythms,such as those caused by atrial or ventricular fibrillation, conductiondisorders or other arrhythmias. A heart rate monitor can measure thenumber of heart contractions per unit of time. A pulse monitor canmeasure the heart rate as felt through the walls of a peripheral artery.A blood pressure sensor can measure systolic, diastolic and meanarterial pressure.

A glucose sensor can provide discrete or continuous measurement of bloodglucose levels.

A drug pump monitor can monitor the dosage and rate of administration ofone or more agents by one or more drug pumps.

A sleep sensor can simultaneously track a number of indicators relatedto the quantity and quality of sleep, such as brain activity, eyemovements, heart rate, muscle tension, oxygen levels, breathingabnormalities and snoring. A sleep monitor can therefore encompassmultiple tests and/or devices, including electroencephalograms,electrooculograms, electrocardiograms, electromyogram, oximeters,breathing sensors and microphones. A REM sleep duration sensor candetect and quantify the period of a user's sleep that is REM (rapid eyemovement) sleep. REM sleep can be detected by measuring eye movementduring sleep using electrooculography, an infrared camera, or any othermethod known in the art.

A still camera can be used to capture and/or record images of one ormore tissues of a user. A video camera can be used to capture and/orrecord sequences of images of one or more tissues of a user constitutingvideos or movies. The still or video cameras can be of any suitablemodality, including visible light and infrared cameras.

A sensor for one or more pharmaceutical agents or pharmaceuticalformulation ingredients can be a sensor for monitoring the systemic orlocal levels of a pharmaceutical agent or ingredient. The sensor can beused to monitor agents that have a narrow therapeutic range, thatexhibit high pharmacokinetic variability or to test novel pharmaceuticalcompounds. For example, the sensor can be a sensor for flecainide,procainamide, digoxin, phenytoin, lithium, valproic acid, gentamicin,amikacin, tacrolimus and/or theophylline.

A sensor for a dissolved gas or ion can be used to measure the local orsystemic levels of gas or ions present in one or more tissues. The gassensor can detect the levels of any gas of interest, such as partialoxygen and carbon dioxide pressures, and nitric oxide levels, thusdetecting hypoxia or other conditions. The ion sensor can measure thelevels of any relevant ions, such as sodium, potassium, calcium,phosphate, zinc, and iron, thus detecting hyper- or hyponatremia, hyper-or hypo hypokalemia, anemia, or other conditions. A pH sensor canspecifically detect hydrogen ions and thus detect acidosis or alkalosis.An ionic strength sensor can measure the concentration of ions in asolution, and an osmolality sensor can measure the body'selectrolyte-water balance. Alone or combined, the aforementioned sensorscan detect a variety of physiological and pathological states accordingto the gas and solute concentration in a tissue, including apnea,dehydration, heart and kidney disease, and diabetes.

All of the above mentioned sensors can detect changes in real timeand/or record data for later retrieval and analysis.

In some embodiments, the actuator can comprise a drug pump, a heartstimulator, a heart pacemaker, a bone growth stimulator, a deep brainstimulator, a neurostimulator, or a neuromuscular electrical stimulator.

A drug pump can be used to control the dosage and rate of local orsystemic administration of one or more agents.

A heart pacemaker can be used to deliver electrical impulses to theheart in order to regulate heart rhythm and rate. A pacemaker can alsobe combined with a defibrillator. A heart stimulator can be programmedto deliver stimulatory impulses to the heart in any specified frequencyand to any specified region.

A bone growth stimulator can be used to assist in any osteogenesisprocess. A bone growth stimulator can be used to accelerate healing ofbone fractures, fusions, or delayed unions by any method known in theart, including via electric or ultrasonic stimulation.

A neurostimulator can used to deliver electric stimulation to targetedbrain areas in order to interfere with neural activity at the targetsite. A neurostimulator can be used to increase or decrease neuronalactivity at the site of interest. A neurostimulator can be a deep brainstimulator.

A neuromuscular stimulator can be used to deliver electrical stimulationthat simulate the action of the central nervous system on muscles. Aneuromuscular stimulator can be used, for example, to improve or recovermuscle function, and for chronic pain management.

In some embodiments, a system can be provided. In some embodiments, asystem can include an RF/ultrasound communication device as describedherein, one or more ultrasound communication devices implantable withina body and capable of ultrasound communication with the communicationdevice. In some embodiments, the RF/ultrasound communication device canbe worn on a skin surface of a body and the one or more ultrasoundcommunication devices are implanted within the body. In someembodiments, an access point device, including a communicationsinterface can be operative to receive and transmit radio frequencytransmissions with the RF/ultrasound communication device. In someembodiments, one or more sensing devices can be a motion sensor, agyroscope, an accelerometer, a cardiac rhythm monitor, a heart ratemonitor, a pulse monitor, a blood pressure monitor, a glucose sensor, adrug pump monitor, a sleep sensor, a REM sleep duration sensor, a stillcamera, a video camera, a sensor for one or more biomolecules, a sensorfor one or more pharmaceutical agents or pharmaceutical formulationingredients, a sensor for a dissolved gas or ion, or a sensor for pH,ionic strength or osmolality. Each sensing device can be incommunication with an ultrasound communication device of the system. Insome embodiments, one or more actuating devices can be a drug pump, aheart stimulator, a heart pacemaker, a bone growth stimulator, a deepbrain stimulator, a neurostimulator, or a neuromuscular electricalstimulator. Each actuating device can be in communication with anultrasound communication device of the system.

In some embodiments, a method can be provided. In some embodiments, amethod can A method of controlling a plurality of networked medicaldevices, the method include providing a system as described hereinincluding one or more sensing devices and/or one or more actuatingdevices, each in communication with an ultrasound communication deviceof the system; configuring the protocol stack and logic device of eachultrasound communication device in the system; acquiring data from theone or more sensing devices and optionally processing the data;optionally communicating the data using the RF/ultrasound communicationdevice, an access point, and the internet to a physician; optionallyreceiving reprogramming instructions using the RF/ultrasoundcommunication device, access point, and internet; reconfiguring theprotocol stack and logic device of one or more selected ultrasoundcommunication devices in the system in response to the reprogramminginstructions; and optionally causing one or more of said actuatingdevices to change their actuation state.

In some embodiments, the reprogramming instructions can include alteringone or more of a data acquisition rate, a data transmission rate, and atype of data sensed by one or more of said sensing devices. In someembodiments, the reprogramming instructions can include one or more ofaltering a parameter, a duty cycle, and a state of one or more of saidactuating devices. In some embodiments, the reprogramming instructionscan include altering one or more of a dosage and a rate ofadministration of one or more agents. In some embodiments, thereprogramming instructions can include altering an instruction to one ormore of said sensing devices or said actuating devices in response to afeedback algorithm. In some embodiments, the reprogramming instructionscan include altering an instruction to one or more of said sensingdevice or said actuating devices in response to a physiological orpathological state of a patient. In some embodiments, the reprogramminginstructions can include triggering a reading from one or more of saidsensing devices or said actuating devices and processing the reading. Insome embodiments, the reprogramming instructions can include altering aninstruction to adjust at runtime a core clock frequency according to aprocessing power requirement, select a low-power mode, provide anautomatic wake-up, or power up or shut down instruction.

The system and method described herein can be used with humans andnon-human animals and can be used in medical and veterinary fields.

The processing unit and communication unit described herein can be partof a computer system that executes programming for controlling thesystem for transmitting data ultrasonically among wearable devices asdescribed herein. The computing system can be implemented as or caninclude a computing device that includes a combination of hardware,software, and firmware that allows the computing device to run anapplications layer, including the application layer described above, orotherwise perform various processing tasks. Computing devices caninclude without limitation personal computers, work stations, servers,laptop computers, tablet computers, mobile devices, hand-held devices,wireless devices, smartphones, wearable devices, smart watches, smartclothing, embedded devices, microprocessor-based devices,microcontroller-based devices, programmable consumer electronics,mini-computers, main frame computers, and the like.

The computing device can include a basic input/output system (BIOS) andan operating system as software to manage hardware components,coordinate the interface between hardware and software, and manage basicoperations such as start up. The computing device can include one ormore processors and memory that cooperate with the operating system toprovide basic functionality for the computing device. The operatingsystem provides support functionality for the applications layer andother processing tasks. The computing device can include a system bus orother bus (such as memory bus, local bus, peripheral bus, and the like)for providing communication between the various hardware, software, andfirmware components and with any external devices. Any other type ofarchitecture or infrastructure that allows the components to communicateand interact with each other can be used.

Processing tasks can be carried out by one or more processors. Varioustypes of processing technology can be used, including a single processoror multiple processors, a central processing unit (CPU), multicoreprocessors, parallel processors, or distributed processors. Additionalspecialized processing resources such as graphics (e.g., a graphicsprocessing unit or GPU), video, multimedia, or mathematical processingcapabilities can be provided to perform certain processing tasks.Processing tasks can be implemented with computer-executableinstructions, such as application programs or other program modules,executed by the computing device. Application programs and programmodules can include routines, subroutines, programs, drivers, objects,components, data structures, and the like that perform particular tasksor operate on data. Real time responses can depend on the environmentand the application or task being performed or updated. In someembodiments, can be on the order of seconds, milliseconds, ormicroseconds.

Processors can include one or more logic devices, such as small-scaleintegrated circuits, programmable logic arrays, programmable logicdevice, masked-programmed gate arrays, field programmable gate arrays(FPGAs), and application specific integrated circuits (ASICs). Logicdevices can include, without limitation, arithmetic logic blocks andoperators, registers, finite state machines, multiplexers, accumulators,comparators, counters, look-up tables, gates, latches, flip-flops, inputand output ports, carry in and carry out ports, and parity generators,and interconnection resources for logic blocks, logic units and logiccells. Although certain embodiments are described above utilizing FPGAs,it will be appreciated that other logic devices, including programmablelogic devices and application specification integrated circuits (ASICs)can be used in some embodiments.

The computing device includes memory or storage, which can be accessedby the system bus or in any other manner. Memory can store controllogic, instructions, and/or data. Memory can include transitory memory,such as cache memory, random access memory (RAM), static random accessmemory (SRAM), main memory, dynamic random access memory (DRAM), andmemristor memory cells. Memory can include storage for firmware ormicrocode, such as programmable read only memory (PROM) and erasableprogrammable read only memory (EPROM). Memory can include non-transitoryor nonvolatile or persistent memory such as read only memory (ROM),memory chips, and memristor memory cells. Non-transitory memory can beprovided on an external storage device. A computer-readable medium caninclude any physical medium that is capable of encoding instructionsand/or storing data that can be subsequently used by a processor toimplement embodiments of the method and system described herein. Anyother type of tangible, non-transitory storage that can provideinstructions and/or data to a processor can be used in theseembodiments.

The computing device can include one or more input/output interfaces forconnecting input and output devices to various other components of thecomputing device. Input and output devices can include, withoutlimitation, keyboards, mice, joysticks, microphones, displays,touchscreens, monitors, scanners, speakers, and printers. Interfaces caninclude universal serial bus (USB) ports, serial ports, parallel ports,game ports, and the like. Other hardware components and devices caninterface with the computing device. As used herein, the term“transceiver” can include one or more devices that both transmit andreceive signals, whether sharing common circuitry, housing, or a circuitboard, or whether distributed over separated circuitry, housings, orcircuit boards, and can include a transmitter-receiver.

The computing device can access a network over a network connection thatprovides the computing device with telecommunications capabilities.Network connection enables the computing device to communicate andinteract with any combination of remote devices, remote networks, andremote entities via a communications link. The communications link canbe any type of communication link, including without limitation a wiredor wireless link. For example, the network connection can allow thecomputing device to communicate with remote devices over a network,which can be a wired and/or a wireless network, and which can includeany combination of intranet, local area networks (LANs), enterprise-widenetworks, medium area networks, wide area networks (WANs), the Internet,cellular networks, and the like. Control logic and/or data can betransmitted to and from the computing device via the network connection.

The computing device can include a browser and a display that allow auser to browse and view pages or other content served by a web serverover the communications link. A web server, server, and database can belocated at the same or at different locations and can be part of thesame computing device, different computing devices, or distributedacross a network. A data center can be located at a remote location andaccessed by the computing device over a network.

IV. EXAMPLES

Prototypes of the embodiments of the IoMT-mote and IoMT-patch describedabove were fabricated. In this section, a performance evaluation of theultrasonic wireless interface implemented on the prototypes is presentedin terms of communication reliability and energy consumption. Theultrasonic wireless interface was responsible for enablingcommunications between the IoMT-patch and the implanted IoMT-mote, andtherefore its performance directly affected life-time of the implantabledevice, the most energy constrained device in the system. The ultrasonicwireless interface performance was also compared with the performance ofan RF wireless interface based on the TI CC2650 BLE MCU when used forintra-body transmissions.

More particularly, the performance of the ultrasonic connectivityoffered by the IoMT devices has been evaluated in terms of energyconsumption and communication reliability using ultrasonic phantoms andporcine meat as communication media, and compared againststate-of-the-art low-power RF-based wireless technologies operating inthe unlicensed industrial, scientific, and medical (ISM) 2.4 GHz band,e.g., Bluetooth Low Energy (BLE). The ISM band is the RF band of choicefor many future wireless medical devices. In fact, using standardtechnologies in the ISM band allows the interface of medical deviceswith commercial devices such as smartphones and tablets. Moreover, theISM band offers larger bandwidth than other bands for medicalapplications, e.g., MedRadio, thus enabling a larger number of devicesoperating simultaneously. Also, the ISM band is internationally(un)regulated offering a larger market to medical device manufacturers.Because of the limitations of RF propagation in human tissue, RF-basedtechnologies are not the best choice for intra-body communications,while ultrasonic waves offer higher reliability with much lower powertransmission. For this reason, in the system architecture describedherein, the use of RF-technology is limited to the out-the-body portionof the system. Specifically, it has been shown that ultrasonic waves canbe efficiently generated and received with low-power and mm-sizedcomponents, and that despite the conversion loss introduced byultrasonic transducers, the gap between RF and ultrasonic attenuation isstill substantial, e.g., ultrasounds can offer 55 to 80 dB lessattenuation than RF waves over 2 to 12 cm links and much lower energyconsumption. Ultrasonic communications have been shown to require muchlower transmission power compared to BLE with equal reliability, e.g.,ultrasounds needs around 35 dBm lower transmission power over 12 cmcommunication distance for 10⁻³ BER leading to lower energy per bit costand longer device lifetime. Finally, it has been shown experimentallythat BLE links are not feasible at all above 12 cm, while ultrasoniclinks can achieve a reliability of 10⁻⁶ up to 20 cm with less than 0 dBmtransmission power.

Example 1: Hardware Energy Consumption

In this section, the energy consumption of the hardware of the IoMT-moteprototype is presented. Measurements were performed using a customcurrent sensing system based on the shunt resistor method. The shuntresistor method comprised sensing a current by measuring voltage dropalong a small resistor, i.e., the shunt resistor, connected in seriesbetween the power supply and the load, i.e., the device under test(DUT). By dividing the voltage drop by the value of the shunt resistor,I=V/R, the current flowing through the resistor, and thus the currentdrawn by the DUT, was obtained. FIG. 11 shows a diagram of themeasurement setup. In this setup, the voltage drop was measured usingtwo analog inputs of the Saleae Logic Pro 8 logic analyzer to capturevoltages at the two ends of a 1Ω shunt resistor. The voltage measures,sampled at 12.5 MHz, were saved on a host computer and exported toMatlab for processing; the voltage drop was obtained as the differencebetween the two voltage measures, and the current flowing through the 1Ωshunt resistor was equal to the voltage difference. Power was suppliedby a DC supply, Instek GPS-4303.

MCU Power Consumption.

In Table II, the current and power consumption of the MCU is reported indifferent operation modes measured using the EEMBC energy measuringtool. Header J10 on the FRDM-KL03Z provided a convenient test point formeasuring the MCU energy consumption. Specifically, the device wasconsidered in RUN and WAIT modes both at 48 MHz and 3 MHz, in STOP,very-low-power stop (VLPS) mode and very-low-leakage (VLL0) mode. Powermeasures were obtained multiplying the current measures for the voltagesupply, 3.3V.

TABLE II Current and Power consumption of the MCU in different states.State Current (mA) Power (mW) RUN @ 48 MHz 6.6 21.78 WAIT @ 48 MHz 2.99.57 RUN @ 3 MHz 1.8 5.4 WAIT @ 3 MHz 1.2 3.6 STOP 0.16 0.528 VLPS 0.0050.0165 VLLS0 <0.001 <0.003

In RUN mode the MCU operated at its maximum performance and consumedaround 6.6 mA at 48 MHz. Every time there no tasks were scheduled,μTasker switched automatically to a low-power mode. By default, the MCUwent into WAIT mode where all the peripherals function while the core isin Sleep mode, reducing the current drawn to 1 to 1.4 mA. As soon as atask was scheduled, an internal interrupt brought the MCU back to RUNmode. When less processing power was needed in RUN mode, e.g., when theMCU just read and stored sensed information, the clock frequency couldbe reduced to lower the power consumption. For example, the MCU drew 1.8mA and 1 mA when under-clocking the system to 3 MHz in RUN and WAITmode, respectively. In STOP mode, the MCU went to deep sleep and all theperipheral clocks were stopped and the chip went static state bringingthe current drawn down to 160 μA. In VLPS mode more peripherals were putto sleep and the current drawn was further reduced to 2.2 μA. Finally,in very-low-leakage stop (VLLS0) mode, all the peripheral including theRAM were shut off, bringing the current drawn down to less than themeasurement sensitivity 1 μA.

FPGA Power and Resource Consumption.

Table III reports the current and power consumption of the differentlogic modules implemented on the FPGA measured using the shunt-resistormeasuring system. The ICE40 Ultra evaluation board offered shuntresistors test point (TP) for measuring the current consumption of theFPGA core I_(CC), as well as the FPGA I/O pins I_(CCIO). Specifically,I_(CC) was measured across the 1Ω series resistor R38 (TP10 and TP11).I_(CCIO) was obtained as the sum of the current consumption of the threebanks of I/O, which can be measured across the 1Ω series resistor R14(TP1 and TP2), R96 (TP8 and TP9) and R96 (TP3 and TP4). Table III alsocompares the measured code and I/O pin currents with the estimated onesÎ_(CC) and Î_(CCIO), obtained using the power estimator software tooloffered by Lattice Semiconductor.

The current consumption for the SPI slave module (MCU interface),transmitter logic processing, the SPI master module (ADC interface), andthe receiver logic processing were isolated. Power measures wereobtained multiplying the current measures for the voltage supply, 1.2 Vfor the FPGA core and 3.3 V for the I/O pins The SPI Slave moduleconsumed around 0.3 mA, and it was activated only for a short period oftime during configuration of the PHY layer parameter and the exchange ofbyte between the FPGA and the MCU before transmitting, and afterreceiving a packet. The transmitter logic, which received data from theMCU and transformed bits into waveforms, consumed around 0.6 mA forprocessing, plus 1 mA of I_(CCIO) when transmitting at the maximumtransmission power, i.e., around 5 dBm. The SPI Master, running at 72MHz to interface the FPGA with the ADC, consumed around 1.5 mA whenactive. The receiver logic operations, which comprised packet detection,synchronization, and bit decoding, consumed around 0.8 mA. The overallreceiver logic consumption was about 2.3 mA during receiving operations.

TABLE III Current and power consumption of hardware components for Tx,Rx and Idle state Module I_(cc) (mA) I_(ccio) (mA) I_(tot) (mA) P_(tot)(mW) SPI Slave 0.3 0 0.3 0.4 Tx Logic 0.6 1 1.6 4 SPI Master 0.7 0.8 1.53.5 Rx Logic 0.8 0 0.8 1 Tot Tx 0.6 1 1.6 4 Tot Rx 1.5 0.3 2.3 4.4

Total Power Consumption.

Table IV reports the current and power consumption of the IoMT-mote,considering the MCU, the FPGA, the ADC, and the receiver preamplifier.The MCU running a 3 MHz was considered, and the node was considered tobe in Tx or Rx mode. The Tx logic was assumed to turn off whenreceiving, and the Rx logic when transmitting through clock gating. Thetransmitter power consumption reported in the table assume 5 dBmtransmission power. Varying the transmission power from −25 dBm to 5dBm, the transmitter consumed between 2.4 mA and 3.4 mA. The receiverconsumed around 9.1 mA, including the MCU, FPGA, ADC and preamplifierconsumption. Without preamplifier, the receiver current consumption wentdown to around 6.1 mA.

TABLE IV Current and power consumption of hardware components for Tx andRx states Current (mA) Power (mW) Component Tx Rx Tx Rx MCU 1.8 1.8 6 6FPGA 1.6 2.3 4 4.4 ADC — 2 — 6.6 Preamp — 3 — 9 Tot. 3.4 9.1 10  26

Active power consumption during receiving and transmitting operationswas reduced by replacing the FPGA with an application-specificintegrated circuit (ASIC). While it is hard to estimate the energy gainfrom replacing an FPGA with an ASIC, because FPGAs have a very widerange of very different internal architectures that result in non-linearrelationship with ASICs, some studies suggest that the power reductioncan be tenfold. As a drawback, using an ASIC loses the advantages of theFPGA, such as flexibility, time-to-market, and upgrades-in-the-field. Inidle mode, the MCU current in VLLS1 was assumed to be 0.6 μA, while allthe other component were shut down, as discussed in Section II-B2.

Table V compares the IoMT-mote prototype current and power consumptionwith the consumption of the TI CC2650 BLE MCU and the Microsemi ZL70103transceiver that operate in the MICS band. For a fair comparison, theZL70103 transceiver was considered as being controlled by a KL03 MCUrunning a 3 MHz; therefore the power consumption reported in Table Valso includes the MCU power consumption. The MCU of the IoMT-moteprototype running a 3 MHz was considered, and the Rx current consumptionwas shown with and without preamplifier. The three devices were assumedas operating with 5 dBm transmission power. It was observed that theIoMT prototype hardware consumption was comparable with the consumptionof commercial wireless devices.

TABLE V Current and power consumption of the IoMT-mote prototypehardware compared to the TI CC2650 and ZL70103 consumption in Tx and Rxmode. I_(Tx) (mA) I_(Rx) (mA) P_(Tx) (mW) P_(Rx) (mW) IoMT-mote 3.46.1/9.1 10 17/26 CC2650 10.47 6.47 34.5 22.3 ZL70103 7.6 6.8 23.3 20.9These results suggest that ultrasonic waves can be efficiently generatedand received using low-energy and miniaturized components, supportingthe feasibility of miniaturizing the IoMT platform described herein.Moreover, the comparison with RF-based systems suggests that theIoMT-mote can achieve comparable power consumption with commercialdevices.

Example 2: Propagation Loss

FIG. 12 shows attenuation loss in pork meat for RF waves at 2.4 GHz andfor ultrasonic waves at 700 kHz. The attenuation included absorption bytissue, conversion losses and spread losses. Measurements were performedby gradually increasing the amount of pork meat between the transmittingand receiving antenna, or transducer. For the RF measurements, thereceived power was measured by the CC2650 MCU, while for the ultrasonicmeasurements prototype, the received power was measured using the SaleaeLogic Pro 8 logic analyzer. To avoid RF leakages that can affect themeasurement results, the two CC2650 boards were enclosed inside twoFaraday shielding bags to attenuate up to 82 dB the RF leakage andtherefore reduce the undesired effect of in-air RF propagation. FIG. 13shows an example of the RF measurement setup. It was observed that for 2to 12 cm propagation distance, RF attenuation was 55 to 80 dB higherthan the ultrasonic attenuation.

Example 3: Bit-Error-Rate Evaluation

This example describes the performance the UsWB transmission schemeimplementation on the IoMT-mote in terms of bit-error-rate as a functionof the transmission power in different use-case scenarios. Ultrasonicphantoms were used that matched the acoustic properties of differenthuman tissues, e.g., soft tissues, bones, and fluids. Specifically, anupper arm phantom and a thoracic phantom were used. The upper armphantom emulated muscle tissue containing veins with fluid simulatingblood. The thoracic phantom included the mid thoracic spinal segmentcontaining spinal fluid, muscle, skin and other soft tissues. FIG. 14shows the channel impulse response (CIR) of the two consideredscenarios. The point at time=0 ms indicates the instant of transmission;the other points represent the time of arrival of the signal paths. Itwas observed that in the upper arm phantom almost no multipath effectwas experienced, except for a secondary path caused by the reflection ofthe transmitted signal between the surfaces, which in fact requireexactly 3 propagation time to arrive at the receiver. Because of thesoft/hard tissue interface in the thoracic phantom, multipath effect wasevidently stronger.

In these tests, the transmission power was varied, by connectingdifferent attenuators between the FPGA output pin and the transmittertransducer. 1-pad attenuators implemented using purely resistivecomponents that operate as simple voltage divider circuit were used. Byusing the attenuators, the transmission power was varied from 5 dBm (3mW) to −25 dBm (3 μW). For each BER measurement up to 2500 packets of 48bytes were transmitted, i.e., approximately 768 kilobits, containingpseudorandom-generated raw data. This allowed the detection of bit errorrates in the order of 10⁻⁶. Two different hardware setups were alsoconsidered, one that included the AD8338 preamplifier and one that didnot. In both cases, the received signal passed through the signalconditioning circuit based on the TI OPA835.

Upper Arm Phantom.

For these tests, the two transducers were placed facing each other onthe opposite surface of the upper arm phantom along the longestdimension, i.e., 19 cm. Mechanical coupling between the transducers andthe phantom was achieved applying a water-based gel between thesurfaces. The overall path loss between the transmitter and receiver wasaround 50 dB. The path loss included conversion loss of the twotransducers, i.e., 12 dB, attenuation due to the tissue absorption andinterface between tissue and fluid, and coupling loss cause by non-idealimpedance matching between the transducer surface and the phantom. FIG.15 shows the setup for this set of experiments.

FIG. 16 shows the BER as a function of the transmission power, for codelength varying in {1,2,3,4,5} and frame length equal to 1 (center) and 2(top), when no preamplifier was used. In this setup, there was verylittle noise measured at the receiver, and the system was limited by thereceiver sensitivity. Without preamplifier, the receiver sensitivity waslimited by the ADC resolution, which set the sensitivity of −62 dBV. Atransmission power of −17 dBm gave a received voltage of −61 dBV, whichwas basically at the limit of the system sensitivity. If thetransmission power were further decreased, the received signal would gobelow the receiver sensitivity, and become so distorted thatsynchronization failed and BER was very high. From these plots, it canbe observed that the BER is a decreasing function of the SNR, and thatthe pseudo-random spreading code scheme mitigated the signal distortion,thus lowering the channel errors. However, increasing the code lengthsdecreased the data rate.

Increasing the frame length should not decrease the BER, since themultipath effect was limited and there were no interfering nodes in thechannel. However, it was observed that changing the frame length from 1to 2 lowered the BER. This happened because the frame increase reducedthe effects of inter-symbol interference (ISI) of pulses overlappingwith pulses in the consecutive time slot caused by the bandwidthlimitation of the transducers. To further investigate this phenomenon,in FIG. 16 (bottom) the BER was plotted as a function of the SNR forframe length varying in {1,2,3,4,5} and code length equal to 2. It wasobserved, as expected, that increasing the frame length gave noadvantage in terms of BER, except for the step 1-2, where the ISI effectcaused by the transducers was predominant.

In the considered setup, the prototype achieved 90 kbit/s, with codelength equals to 1 and frame length equals to 2, i.e., pair (1,2) with a10⁻⁶ BER with an input power at the Tx transducer of about −10 dBm (0.1mW). A data rate up to about 180 kbit/s could be achieved (also with10⁻⁶ BER) with a (1,1) pair increasing the input power to 0 dBm (1 mW).Lower-power transmissions were also possible by compensating with longerspreading code. For example, in the current implementation, for a Txpower of −15 dBm (30 μW), and with a code length of 5 and frame lengthof 2, a data rate of 18 kbit/s was obtained with a BER lower than 10⁻⁶.Longer codes could be used for lower data rate and lower powertransmissions, e.g., current implementation allowed up to code length 15that led to a data rate of 6 kbit/s with frame length equal to 2.However, without using a preamplifier at the receiver, the minimumtransmission power achievable was limited by the receiver sensitivity of−62 dBV.

Thoracic Phantom.

Because of the spinal segment, with this phantom the systemcommunication performance through heterogeneous soft/hard tissue mediumcould be tested. For these tests, the two transducers were placed facingeach other, 19 cm apart. The overall path loss between the transmitterand receiver was around 60 dB. The additional 10 dB loss compared to theupper arm setup was given by the higher attenuation due to the bonetissue, as well as the interface between soft/hard tissue and cerebralspinal fluid. For this set of experiments the preamplifier setup wasused. FIG. 17 shows the setup for this set of experiments.

FIG. 18 shows the BER as a function of the transmission power for frameequal to 2, code length equal to 1 and 2, for different value ofamplification gain at the receiver. FIG. 18 (bottom) compares these BERcurves to the BER curves obtained in the 0-gain scenario when nopreamplifier is used. We observe that an increase of 10 dBm intransmission power was needed to achieve the same BER performance of theupper arm scenario. This was because of the higher path loss as well asthe higher multipath effect, as shown in FIG. 14. Again, at least a 40dB gain was required for the preamplifier setup to outperform theno-amplifier setup. Moreover, because of the higher attenuation causedby the bone, without preamplifier a BER could only be achieved on theorder of 10⁻⁵ with a pair (1,2), i.e., 90 kbit/s data rate, and with atransmission power of 5 dBm. In order to lower the BER, or to furtherincrease the data rate to 180 kbit/s with pair (1,1), highertransmission power was needed. On the other hand, using the preamplifierwith 40 dB gain and 50 dB gain, 90 kbit/s with 10⁻⁶ BER was achievablewith 0 dBm and −8 dBm transmission power, respectively.

Whether to use the preamplifier or not depends on the applicationscenario considered, and it should account for other designrequirements. Without the preamplifier, the 3 mA current that powers thepreamplifier could be used to get an additional 10 dBm of thetransmission power at the transmitter. Without using the preamplifierand increasing the transmission power, the power consumption could bebalanced between the transmitter and receiver, which can be useful forenergy fairness and network lifetime. Also, without the preamplifier,the size and the complexity of the design can be reduced, which can beanother consideration for the system. On the other hand, using the 3 mAfor the preamplifier can provide up to 60 dB gain at the receiver anddrastically lower the transmission power.

Example 4: BLE v. UsWB

Packet-Error-Rate (PER).

UsWB transmission scheme implemented in the IoMT-mote was compared withthe BLE physical layer based on a 1 Mbit/s Gaussian frequency shift key(GFSK) implemented on the TI CC2650 in terms of reliability (PER)through pork meat. Pork meat closely emulates human muscular tissues andallowed the testing of both ultrasonic and RF-based communication sideby side and evaluation of their performance in terms of reliability andenergy consumption. For the IoMT-mote evaluation, a setup was consideredwhere ultrasonic transducers were facing each other 12 cm apart, asshown in FIG. 19. For these experiments, a 50 dB gain was set at thereceiver preamplifier. For the BLE evaluation, the TI SmartRF softwaretool was used to evaluate the PER performance of a BLE communicationbetween two CC2650 BLE devices by transmitting 1000 32-bytes packet. ThePER was obtained as the ratio between the number of packets receivedwith errors, or not received at all, and the total number of packetstransmitted. FIG. 20 (top) shows the UsWB PER as a function of thetransmission power (dBm), for code and frame length in {1,2}. For 10⁻⁶BER, the prototype achieved 180 kbit/s, pair (1,1), with code and framelength equal to 1, with a transmission power of about −20 dBm (10 μW).By using frame length equals to 2 to get rid of the ISI effect, a 90kbit/s data rate was achieved, with the same 10⁻⁶ BER constraint, andtransmission power of −27 dBm (2 μW). FIG. 20 (center) shows the PERperformance of BLE in pork meat as a function of the transmission powerfor different communication distances. It can be observed that forlonger distances higher transmission power was required, and fordistances longer than 10 cm, reliability performance droppeddramatically. Specifically, for 12 cm distance, the PER became as highas 80% with the maximum transmission power available, i.e., 5 dBm,making communication almost unfeasible. With higher distances, thecommunication was completely disrupted, i.e., 100% PER.

In FIG. 20 (bottom), PER performance of BLE over a 12 cm distance wascompared with the IoMT-mote performance (code and frame length equals to1). It was observed that BLE required around 35 dBm higher transmissionpower to achieve the same reliability of UsWB. This gap can be furtherincreased by implementing stronger synchronization and decodingoperations in the UsWB PHY implementation. The lower transmission power,together with the lower absorption in tissues compared to RF stronglyreduced any potential thermal effect caused by the increase of bodytemperature that could determine adverse effects.

Energy per Bit and Device Lifetime.

A remote monitoring application was considered in which a 20-byteinformation packet must be sent at least every minute between twodevices. Specifically, a master node wanted to retrieve the informationdata from a slave node. 20-byte was selected because it was the maximumamount of application layer data that BLE allowed to be transmitted in asingle LL packet. The energy consumption of the IoMT-mote was comparedwith the energy consumption of the CC2650 BLE devices. Current and powerconsumption values were assumed as reported in Table V, considering theIoMT-prototype. Energy per bit, Eb, was defined as the ratio between thetotal energy spent by the two devices for exchanging information dataover the amount of successfully exchanged information data, and it wasmeasured in J/bit. Network lifetime was the minimum between the masterand slave's battery lifetime and it was measured in years.

For the BLE devices, a scenario was considered where the slave nodeinitiated an advertising event every advertising interval T_(a) usingthe three control channels sequentially. The master node connected, andthe connection stayed open with a connection event happening every 32 s,i.e., the maximum connection interval available. In the following, itwas assumed both devices were operating at 5 dBm transmission power,unless otherwise specified. Based on this scenario, the BLE devicesconsumed around 123 μJ for a data exchange, and therefore the energy perbit is equal to 0.77 μJ/bit. The IoMT-motes consumed around 57.4 μJ foreach data exchange, and therefore the energy per bit is equal to 0.37μJ/bit.

To evaluate the two systems in terms of device lifetime, transmitting,receiving, processing and idle states only were considered. Processingstate occurred before and after a packet transmission and reception, and0.5 ms interval with a consumption of 3 mA was assumed. 2 μA idlecurrent consumption, and a 300 mAh battery were also assumed. Underthese conditions, the BLE network lifetime was 12.5, against 14.8 yearsachieved by the UsWB. Note that these results were based on the hardwareconsumption and the LL protocol operations only. In the following, it isshown how these results were affected when considering the propagationand reliability characteristics of the two systems.

FIG. 21 shows the energy per bit (top) and the network lifetime (bottom)using the PER values obtained from the experiments discussed above. Itcan be observed how over 12 cm UsWB outperformed BLE in terms oflifetime and energy per bit. In fact, UsWB can achieve much lower PERwith lower transmission power, and therefore keep the energy per bit andnetwork lifetime close to the ideal values of 14.8 years achieved whenBER is ideally zero. On the other hand, BLE can only operate over 12 cmat the maximum transmission power, still underperforming in terms of BERcompared to UsWB. This further reduces the network lifetime and increasethe energy cost for transmitting an information bit. Specifically, UsWBallows almost two more years of operations while achieving much higherreliability than BLE, i.e., about three order of magnitude lower PER.FIG. 21 shows how the UsWB energy per bit and lifetime performance wouldscale if the data rate were increased from 180 kbit/s to 1 Mbit/s tomatch the BLE data rate. This can be achieved using ultrasonictransducers with higher bandwidth and/or using higher order modulationschemes. Results show how energy per bit can become as low as 0.07μJ/bit and network lifetime increase up to 16 years.

As used herein, “consisting essentially of” allows the inclusion ofmaterials or steps that do not materially affect the basic and novelcharacteristics of the claim. Any recitation herein of the term“comprising,” particularly in a description of components of acomposition or in a description of elements of a device, can beexchanged with “consisting essentially of” or “consisting of.”

It will be appreciated that the various features of the embodimentsdescribed herein can be combined in a variety of ways. For example, afeature described in conjunction with one embodiment may be included inanother embodiment even if not explicitly described in conjunction withthat embodiment.

To the extent that the appended claims have been drafted withoutmultiple dependencies, this has been done only to accommodate formalrequirements in jurisdictions which do not allow such multipledependencies. It should be noted that all possible combinations offeatures which would be implied by rendering the claims multiplydependent are explicitly envisaged and should be considered part of theinvention.

The present invention has been described in conjunction with certainpreferred embodiments. It is to be understood that the invention is notlimited to the exact details of construction, operation, exact materialsor embodiments shown and described, and that various modifications,substitutions of equivalents, alterations to the compositions, and otherchanges to the embodiments disclosed herein will be apparent to one ofskill in the art.

What is claimed is:
 1. A method of controlling a plurality of networkedmedical devices, the method comprising the steps of: (a) providing asystem comprising: an RF/ultrasound communication device; one or moreultrasound communication devices implantable within a body and capableof ultrasound communication with the RF/ultrasound communication device,each of the ultrasound communication devices comprising: a communicationunit comprising an ultrasonic transceiver to transmit and receiveultrasonic signals, the communication unit configured to transmit andreceive the ultrasonic signals through biological tissue to and fromcommunication units of other implanted or wearable medical devices inthe network of devices, and a processing unit in communication with thecommunication unit, the processing unit including a core unitcomprising: a logic device including a physical layer of a protocolstack, and a controller unit including upper layers of the protocolstack, the upper layers including at least a link layer and anapplication layer, the controller unit further including a dataprocessing module at the application layer for communication with asensor or actuator, wherein the link layer is connected with the logicdevice to send parameters to the physical layer for transmission ofultrasonic signals through the biological tissue and with the dataprocessing module to transfer data or parameters to or from the sensoror actuator, and wherein the processing unit further comprises an energymanagement module operative to adjust power usage based on operatingrequirements by automatically sending signals to wake-up, power up, shutdown electronic components, to adjust at runtime a core clock frequencyaccording to processing power required, and to select at runtime alow-power mode; and one or more sensing devices and/or one or moreactuating devices, each in communication with one of the ultrasoundcommunication devices of the system; (b) configuring the protocol stackand logic device of each ultrasound communication device in the system;(c) acquiring data from the one or more sensing devices and optionallyprocessing the data; (d) optionally communicating the data using theRF/ultrasound communication device, an access point, and the internet toa physician; (e) optionally receiving reprogramming instructions usingthe RF/ultrasound communication device, access point, and internet; (f)optionally reconfiguring the protocol stack and logic device of one ormore selected ultrasound communication devices in the system in responseto the reprogramming instructions; and (g) optionally causing one ormore of said actuating devices to change their actuation state.
 2. Anultrasound communication device for transmitting signals ultrasonicallywithin a network of implanted and/or wearable medical devices,comprising: a communication unit comprising an ultrasonic transceiver totransmit and receive ultrasonic signals, the communication unitconfigured to transmit and receive the ultrasonic signals throughbiological tissue to and from other communication units of otherimplanted or wearable medical devices in the network of devices; and aprocessing unit in communication with the communication unit, theprocessing unit including a core unit comprising: a logic deviceincluding a physical layer of a protocol stack, and a controller unitincluding upper layers of the protocol stack, the upper layers includingat least a link layer and an application layer, the controller unitfurther including a data processing module at the application layer forcommunication with a sensor or actuator, wherein the link layer isconnected with the logic device to send parameters to the physical layerfor transmission of ultrasonic signals through the biological tissue andwith the data processing module to transfer data or parameters to orfrom the sensor or actuator; and wherein the processing unit furthercomprises an energy management module operative to adjust power usagebased on operating requirements by automatically sending signals towake-up, power up, shut down electronic components, to adjust at runtimea core clock frequency according to processing power required, and toselect at runtime a low-power mode.
 3. The device of claim 2, whereinthe reconfigurable logic device further comprises transmitter chainblocks to output a train of pulses following a predefined time-hoppingpattern and receiver chain blocks to decode ultrasonic transmissionsreceived from the communication unit and deliver a stream of binary datato the controller unit.
 4. The device of claim 2, wherein thereconfigurable logic device includes a register module operative tostore configuration parameters received from the controller unit and toroute the configuration parameters to one or more modules within thereconfigurable logic device, the configuration parameters including oneor more of a spreading code, a spreading code length, a time-hoppingframe length, a time-hopping sequence, a packet payload size, or alength of a preamble.
 5. The device of claim 2, wherein thereconfigurable logic device includes a configurable serial peripheralinterface (SPI) module in communication with the controller unit.
 6. Thedevice of claim 5, wherein the SPI module is operative to configurecommunication settings, including one or more of data rate, clockpolarity and clock phase.
 7. The device of claim 5, wherein the SPImodule is operative to enable communication with the processor or aperipheral device.
 8. The device of claim 5, wherein the SPI moduleincludes a master module in communication with the processor and a slavemodule.
 9. The device of claim 5, wherein the SPI module is operative totrigger sampling operations on an analog to digital converter and toread back sampled digital waveforms.
 10. The device of claim 2, whereinthe reconfigurable logic device includes a field-programmable gatearray, a masked-programmed gate array, an application specificintegrated circuit, a small-scale integrated circuit, a programmablelogic array, or a programmable logic device.
 11. The device of claim 2,further comprising a sensing or actuating unit, and wherein thecontroller unit is operative in real time to trigger a reading from thesensing or actuating unit and to process the reading and is furtheroperative to transmit data processed from the reading to thereconfigurable logic device for transmission as an ultrasonic signal.12. The device of claim 2, wherein the core unit is operative toreconfigure one or more of the application layer, the link layer, amedia access control layer, and a network transport layer of theprotocol stack.
 13. The device of claim 2, further comprising a sensorinterface to enable connection between the processing unit and a sensordevice or an actuating device.
 14. The device of claim 2 incommunication with a sensing device selected from the group consistingof a motion sensor, a gyroscope, an accelerometer, a cardiac rhythmmonitor, a heart rate monitor, a pulse monitor, a blood pressuremonitor, a glucose sensor, a drug pump monitor, a sleep sensor, a REMsleep duration sensor, a still camera, a video camera, a sensor for oneor more biomolecules, a sensor for one or more pharmaceutical agents orpharmaceutical formulation ingredients, a sensor for a dissolved gas orion, a sensor for pH, a sensor for ionic strength, and a sensor forosmolality.
 15. The device of claim 2 in communication with an actuatingdevice selected from the group consisting of a drug pump, a heartstimulator, a heart pacemaker, a bone growth stimulator, a deep brainstimulator, a neurostimulator, and a neuromuscular electricalstimulator.
 16. The device of claim 2, wherein the device is implantablewithin a body or wearable on a skin surface of a body.
 17. The device ofclaim 2, wherein the communication unit further includes a radiofrequency (RF) interface operative to receive and transmit in-air RFtransmissions, and wherein the device is wearable on a skin surface of abody.
 18. The device of claim 17, wherein the device is in communicationvia said RF transmissions with a further device coupled to acommunications network.
 19. The device of claim 18, further comprising awireless controller is operative connect to a Bluetooth Low Energy (BLE)access point device and/or to a 6LoWPAN device.
 20. The device of claim18, wherein the wireless controller includes a Message Queue TelemetryTransport (MQTT) client module that is operative to read data from theimplantable device through the ultrasonic interface, publish sensorreadings to an MQTT broker, open a connection with the MQTT brokerthrough an IPv6 address, authenticate an application, and/or publish newcontent.
 21. A system comprising: an RF/ultrasound communication device;and one or more ultrasound communication devices of claim 2 implantablewithin a body and capable of ultrasound communication with theRF/ultrasound communication device.